Fungicidal pyrazoles

ABSTRACT

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, 
                         
wherein
         Q 1  is a phenyl ring, naphthalenyl ring system, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure;   Q 2  is a phenyl ring, a naphthalenyl ring system, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring, or an 8- to 10-membered heteroaromatic bicyclic ring system, each as described with optional substituents as defined in the disclosure;   X is O, S(O) m , NR 4 , CR 15 R 16 , C(═O) or C(═S);   and R 1 , R 1a , R 2 , R 4 , R 15 , R 16  and m are as defined in the disclosure.       

     Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention. Also disclosed are compounds of Formula 2, including all geometric and stereoisomers, and salts thereof, 
                         
wherein
         X is NH; and   Q 1 , Q 2  and R 2  are as defined for Formula 1;
 
which are useful as intermediates for preparing compounds of Formula 1.

FIELD OF THE INVENTION

This invention relates to certain pyrazoles, their N-oxides, salts and compositions, and methods of their use as fungicides.

BACKGROUND OF THE INVENTION

The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different sites of action. JP09208620 discloses N-phenylpyrazolylamine and N-pyridylpyrazolylamine derivatives as insecticides, herbicides and fungicides; however the fungicides of the present invention are not disclosed in this publication.

SUMMARY OF THE INVENTION

This invention is directed to compounds of Formula 1 (including all geometric and stereoisomers), N-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:

wherein

-   -   Q¹ is a phenyl ring or a naphthalenyl ring system, each ring or         ring system optionally substituted with up to 5 substituents         independently selected from R³; or a 5- to 6-membered fully         unsaturated heterocyclic ring or an 8- to 10-membered         heteroaromatic bicyclic ring system, each ring or ring system         containing ring members selected from carbon atoms and up to 4         heteroatoms independently selected from up to 2 O, up to 2 S and         up to 4 N atoms, wherein up to 3 carbon ring members are         independently selected from C(═O) and C(═S), and the sulfur atom         ring members are independently selected from         S(═O)_(u)(═NR¹⁴)_(v), each ring or ring system optionally         substituted with up to 5 substituents independently selected         from R³ on carbon atom ring members and selected from cyano,         C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl,         C₁-C₆ alkoxy, C₂-C₆ alkoxyalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆         alkoxycarbonyl, C₂-C₆ alkylaminoalkyl and C₃-C₆         dialkylaminoalkyl on nitrogen atom ring members;     -   Q² is a phenyl ring or a naphthalenyl ring system, each ring or         ring system optionally substituted with up to 5 substituents         independently selected from R³; or a 5- to 6-membered saturated,         partially unsaturated or fully unsaturated heterocyclic ring or         an 8- to 10-membered heteroaromatic bicyclic ring system, each         ring or ring system containing ring members selected from carbon         atoms and up to 4 heteroatoms independently selected from up to         2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon ring         members are independently selected from C(═O) and C(═S), and the         sulfur atom ring members are independently selected from         S(═O)_(u)(═NR¹⁴)_(v), each ring or ring system optionally         substituted with up to 5 substituents independently selected         from R³ on carbon atom ring members and selected from cyano,         C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl,         C₁-C₆ alkoxy, C₂-C₆ alkoxyalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆         alkoxycarbonyl, C₂-C₆ alkylaminoalkyl and C₃-C₆         dialkylaminoalkyl on nitrogen atom ring members; or C₁-C₁₂         alkyl, C₂-C₁₂ alkenyl, C₂-C₁₂ alkynyl, C₃-C₁₂ cycloalkyl or         C₃-C₁₂ cycloalkenyl, each optionally substituted with up to 5         substituents independently selected from R³;     -   X is O, S(O)_(m), NR⁴, CR¹⁵R¹⁶, C(═O) or C(═S);     -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₄ alkenyl,         C₂-C₄ alkynyl, C₃-C₇ cycloalkyl, CO₂R⁵, C(O)NR⁶R⁷, cyano, C₁-C₆         alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl; or     -   R¹ is phenyl optionally substituted with up to 3 R⁸; or a five-         or six-membered nitrogen-containing aromatic heterocycle         optionally substituted with up to 3 substituents independently         selected from R^(9a) on carbon atom ring members and R^(9b) on         nitrogen atom ring members;     -   R^(1a) is H; or     -   R^(1a) and R¹ are taken together with the carbon atom to which         they are attached to form a cyclopropyl ring optionally         substituted with up to 2 substituents independently selected         from halogen and methyl;     -   R² is CH₃, CH₂CH₃, halogen, cyano, cyanomethyl, halomethyl,         hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally         substituted with up to 2 substituents independently selected         from halogen and methyl;     -   each R³ is independently selected from halogen, cyano, nitro,         amino, methylamino, dimethylamino, formylamino, C₂-C₃         alkylcarbonylamino, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy,         C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₃         alkylsulfinyl, C₁-C₃ haloalkylsulfinyl, C₁-C₃ alkylsulfonyl,         C₁-C₃ haloalkylsulfonyl, C₁-C₂ alkylsulfonyloxy, C₁-C₂         haloalkylsulfonyloxy, C₃-C₄ cycloalkyl, C₃-C₇ cycloalkoxy, C₄-C₆         alkylcycloalkyl, C₄-C₆ cycloalkylalkyl, C₃-C₇ halocycloalkyl,         C₂-C₄ alkenyl, C₂-C₄ alkynyl, hydroxy, formyl, C₂-C₃         alkylcarbonyl, C₂-C₃ alkylcarbonyloxy, —SF₅, —SCN, C(═S)NR¹⁹R²⁰         or —U—V-T;     -   R⁴ is H, formyl, C₂-C₅ alkenyl, C₃-C₅ alkynyl, C₃-C₇ cycloalkyl,         —SO₃ ⁻M⁺, —S(═O)_(t)R¹⁰, —(C═W)R¹¹, NH₂ or OR²¹; or C₁-C₆ alkyl         or C₁-C₆ haloalkyl, each optionally substituted with up to 2         R¹²;     -   R⁵ is H, C₁-C₆ alkyl or C₁-C₆ haloalkyl;     -   R⁶ and R⁷ are independently selected from H, C₁-C₆ alkyl, C₁-C₆         haloalkyl, C₃-C₇ cycloalkyl, C₄-C₈ cycloalkylalkyl and C₄-C₈         alkylcycloalkyl; or     -   R⁶ and R⁷ are taken together with the nitrogen atom to which         they are connected to form a four- to seven-membered nonaromatic         heterocyclic ring containing ring members, in addition to the         connecting ring nitrogen atom, selected from carbon atoms and         optionally up to one ring member selected from O, S(O)_(n) and         NR¹³;     -   each R⁸, R^(9a) and R^(9b) is independently selected from         halogen, C₁-C₂ alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy, C₁-C₂         haloalkoxy, cyano, nitro, SCH₃, S(O)CH₃ and S(O)₂CH₃;     -   R¹⁰ is C₁-C₆ alkyl or C₁-C₆ haloalkyl;     -   each R¹¹ is independently C₁-C₆ alkyl, C₁-C₆ alkoxy, C₂-C₇         alkoxyalkyl, C₂-C₇ alkylaminoalkyl, C₂-C₈ dialkylaminoalkyl,         C₁-C₆ alkylthio or C₂-C₇ alkylthioalkyl;     -   each R¹² is independently C₃-C₇ cycloalkyl, C₁-C₄ alkoxy, C₁-C₄         haloalkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfinyl, C₁-C₄         alkylsulfonyl or cyano;     -   R¹³ is H, C₁-C₃ alkyl or C₂-C₃ haloalkyl;     -   each R¹⁴ is independently H, cyano, C₁-C₃ alkyl or C₁-C₃         haloalkyl;     -   R¹⁵ is H, C₁-C₄ alkyl or OR¹⁸;     -   R¹⁶ is C₁-C₄ alkyl or OR¹⁸; or     -   R¹⁵ and R¹⁶ are taken together as —OCH₂CH₂O—;     -   each R¹⁸ is independently H, formyl, C₃-C₇ cycloalkyl, —SO₃ ⁻M⁺         or —(C═W)R¹¹; or C₁-C₆ alkyl or C₁-C₆ haloalkyl, each optionally         substituted with up to 2 R¹²;     -   each R¹⁹ and R²⁰ is independently H or CH₃;     -   R²¹ is H, formyl, C₃-C₇ cycloalkyl, —SO₃ ⁻M⁺ or —(C═W)R¹¹; or         C₁-C₆ alkyl or C₁-C₆ haloalkyl, each optionally substituted with         up to 2 R¹²;     -   each U is independently O, S(═O)_(w), NR²² or a direct bond;     -   each V is independently C₁-C₆ alkylene, C₂-C₆ alkenylene, C₃-C₆         alkynylene, C₃-C₆ cycloalkylene or C₃-C₆ cycloalkenylene,         wherein up to 3 carbon atoms are independently selected from         C(═O), each optionally substituted with up to 5 substituents         independently selected from halogen, cyano, nitro, hydroxy,         C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy and C₁-C₆ haloalkoxy;     -   each T is independently cyano, NR^(23a)R^(23b), OR²⁴ or         S(═O)_(y)R²⁵     -   each R²² is independently H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆         alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆ (alkylthio)carbonyl,         C₂-C₆ alkoxy(thiocarbonyl), C₄-C₈ cycloalkylcarbonyl, C₄-C₈         cycloalkoxycarbonyl, C₄-C₈ (cycloalkylthio)carbonyl or C₄-C₈         cycloalkoxy(thiocarbonyl);     -   each R^(23a) and R^(23b) is independently H, C₁-C₆ alkyl, C₁-C₆         haloalkyl, C₂-C₆ alkenyl, C₃-C₆ alkynyl, C₃-C₆ cycloalkyl, C₃-C₆         halocycloalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆         (alkylthio)carbonyl, C₂-C₆ alkoxy(thiocarbonyl), C₄-C₈         cycloalkylcarbonyl, C₄-C₈ cycloalkoxycarbonyl, C₄-C₈         (cycloalkylthio)carbonyl or C₄-C₈ cycloalkoxy(thiocarbonyl); or     -   a pair of R^(23a) and R^(23b) attached to the same nitrogen atom         are taken together with the nitrogen atom to form a 3- to         6-membered heterocyclic ring, the ring optionally substituted         with up to 5 substituents independently selected from R²⁶;     -   each R²⁴ and R²⁵ is independently H, C₁-C₆ alkyl, C₁-C₆         haloalkyl, C₂-C₆ alkenyl, C₃-C₆ alkynyl, C₃-C₆ cycloalkyl, C₃-C₆         halocycloalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆         (alkylthio)carbonyl, C₂-C₆ alkoxy(thiocarbonyl), C₄-C₈         cycloalkylcarbonyl, C₄-C₈ cycloalkoxycarbonyl, C₄-C₈         (cycloalkylthio)carbonyl or C₄-C₈ cycloalkoxy(thiocarbonyl);     -   each R²⁶ is independently halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl         or C₁-C₆ alkoxy;     -   each W is independently O or S;     -   each M⁺ is independently a cation;     -   m is 0, 1 or 2;     -   n is 0, 1 or 2;     -   t is 0, 1 or 2;     -   each u and v are independently 0, 1 or 2 in each instance of         S(═O)_(u)(═NR¹⁴)_(v), provided that the sum of u and v is 0, 1         or 2;     -   each w is independently 0, 1 or 2; and     -   each y is independently 0, 1 or 2;         provided that:     -   when Q² is a phenyl ring substituted on at least one ortho         position with a substituent selected from —U—V-T wherein U is a         direct bond, V is C(═O) and T is NR^(23a)R^(23b) or OR²⁴, then X         is other than NR⁴.

More particularly, this invention pertains to a compound of Formula 1 (including all geometric and stereoisomers), an N-oxide or a salt thereof.

This invention also relates to a fungicidal composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

This invention also relates to a fungicidal composition comprising: (a) a compound of Formula 1, an N-oxide, or a salt thereof, and (b) at least one other fungicide (e.g., at least one other fungicide having a different site of action).

This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of the invention (e.g., as a composition described herein).

This invention also relates to a composition comprising a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent.

The invention also relates to compounds of Formula 2 (including all geometric and stereoisomers) and salts thereof

wherein

-   -   X is NH; and     -   Q¹, Q² and R² are as defined above for Formula 1;         provided that:     -   (a) when Q² is a phenyl ring substituted on at least one ortho         position with a substituent selected from —U—V-T wherein U is a         direct bond and T is NR^(23a)R^(23b) or OR²⁴, then V is other         than C(═O); and     -   (b) when Q¹ is phenyl and Q² is 4-(trifluoromethyl)phenyl, then         R² is other than methyl;         and to use of said compounds as intermediates for preparing         compounds of Formula 1. More particularly, the present invention         pertains to a compound of Formula 2 or a salt thereof.

DETAILS OF THE INVENTION

As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.

The transitional phrase “consisting of” excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consisting of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

The transitional phrase “consisting essentially of” is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term “consisting essentially of” occupies a middle ground between “comprising” and “consisting of”.

Where applicants have defined an invention or a portion thereof with an open-ended term such as “comprising,” it should be readily understood that (unless otherwise stated) the description should be interpreted to also describe such an invention using the terms “consisting essentially of” or “consisting of.”

Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

Also, the indefinite articles “a” and “an” preceding an element or component of the invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore “a” or “an” should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

As referred to in the present disclosure and claims, “plant” includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.

As referred to herein, the term “seedling”, used either alone or in a combination of words means a young plant developing from the embryo of a seed.

As used herein, the term “alkylating agent” refers to a chemical compound in which a carbon-containing radical is bound through a carbon atom to leaving group such as halide or sulfonate, which is displaceable by bonding of a nucleophile to said carbon atom. Unless otherwise indicated, the term “alkylating” does not limit the carbon-containing radical to alkyl; the carbon-containing radicals in alkylating agents include the variety of carbon-bound substituent radicals specified for R¹.

Generally when a molecular fragment (i.e. radical) is denoted by a series of atom symbols (e.g., C, H, N, O, S) the implicit point or points of attachment will be easily recognized by those skilled in the art. In some instances herein, particularly when alternative points of attachment are possible, the point or points of attachment may be explicitly indicated by a hyphen (“-”). For example, “—SCN” indicates that the point of attachment is the sulfur atom (i.e. thiocyanato, not isothiocyanato).

In the above recitations, the term “alkyl”, used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. “Alkenyl” includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl isomers. “Alkenyl” also includes polyenes such as 1,2-propadienyl. “Alkynyl” includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl isomers. “Alkenylene” denotes a straight-chain or branched alkenediyl containing one olefinic bond. Examples of “alkenylene” include CH═CH, CH₂CH═CH, CH═C(CH₃). “Alkynylene” denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of “alkynylene” include CH₂C≡C, C≡CCH₂ and the different butynylene, pentynylene and hexynylene isomers.

“Alkoxy” includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. “Alkoxyalkyl” denotes alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH₃OCH₂, CH₃OCH₂CH₂, CH₃CH₂OCH₂, CH₃CH₂CH₂CH₂OCH₂ and CH₃CH₂OCH₂CH₂. “Alkylthio” includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. “Alkylsulfinyl” includes both enantiomers of an alkylsulfinyl group. Examples of “alkylsulfinyl” include CH₃S(O)—, CH₃CH₂S(O)—, CH₃CH₂CH₂S(O)—, (CH₃)₂CHS(O)— and the different butylsulfinyl isomers. Examples of “alkylsulfonyl” include CH₃S(O)₂—, CH₃CH₂S(O)₂—, CH₃CH₂CH₂S(O)₂—, (CH₃)₂CHS(O)₂—, and the different butylsulfonyl isomers. “Alkylthioalkyl” denotes alkylthio substitution on alkyl. Examples of “alkylthioalkyl” include CH₃SCH₂, CH₃SCH₂CH₂, CH₃CH₂SCH₂, CH₃CH₂CH₂CH₂SCH₂ and CH₃CH₂SCH₂CH₂. “(Alkylthio)carbonyl” denotes a straight-chain or branched alkylthio group bonded to a C(═O) moiety. Examples of “(alkylthio)carbonyl” include CH₃SC(═O), CH₃CH₂CH₂SC(═O) and (CH₃)₂CHSC(═O). “Alkoxy(thiocarbonyl)” denotes a straight-chain or branched alkoxy group bonded to a C(═S) moiety. Examples of “alkoxy(thiocarbonyl)” include CH₃OC(═S), CH₃CH₂CH₂OC(═S) and (CH₃)₂CHOC(═S). “Alkylaminoalkyl” denotes a straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino(straight-chain or branched)alkyl moiety. Examples of “alkylaminoalkyl” include CH₃NHCH₂—, (CH₃)₂CHNHCH₂— and CH₃NHCH(CH₃)—. “Dialkylaminoalkyl” denotes two independent straight-chain or branched alkyl moieties bonded to a nitrogen atom of an amino(straight-chain or branched)alkyl moiety. Examples of “dialkylaminoalkyl” include (CH₃)₂NCH₂—, (CH₃)₂CH(CH₃)NCH₂— and (CH₃)₂NCH(CH₃)—. The term “alkylcarbonylamino” denotes alkyl bonded to a C(═O)NH moiety. Examples of “alkylcarbonylamino” include CH₃CH₂C(═O)NH and CH₃CH₂CH₂C(═O)NH.

“Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term “alkylcycloalkyl” denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, i-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term “cycloalkylalkyl” denotes cycloalkyl substitution on an alkyl moiety. Examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. The term “cycloalkoxy” denotes cycloalkyl linked through an oxygen atom such as cyclopentyloxy and cyclohexyloxy. “Cycloalkenyl” includes carbocyclic rings that contain only one double bond such as cyclopentenyl and cyclohexenyl, as well as carbocyclic rings with more than one double bond such as 1,3- and 1,4-cyclohexadienyl, but are not aromatic. “Cycloalkylcarbonyl” denotes cycloalkyl bonded to a C(═O) group including, for example, cyclopropylcarbonyl and cyclopentylcarbonyl. The term “cycloalkoxycarbonyl” means cycloalkoxy bonded to a C(═O) group, for example, cyclopropyloxycarbonyl and cyclopentyloxycarbonyl. The term“cycloalkylene” denotes a cycloalkanediyl ring. Examples of “cycloalkylene” include cyclopropylene, cyclobutylene, cyclopentylene and cyclohexylene. The term“cycloalkenylene” denotes a cycloalkenediyl ring containing one olefinic bond. Examples of “cycloalkenylene” include cylopropenediyl and cyclpentenediyl.

The term “halogen”, either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F₃C—, ClCH₂—, CF₃CH₂— and CF₃CCl₂—. The terms “halocycloalkyl”, “haloalkoxy”, “haloalkylthio”, and the like, are defined analogously to the term “haloalkyl”. Examples of “haloalkoxy” include CH₂FO—, CHF₂O—, CF₃O—, CCl₃CH₂O—, HCF₂CH₂CH₂O— and CF₃CH₂O—. Examples of “fluoroalkoxy” include CH₂FO—, CHF₂O—, CF₃O— HCF₂CH₂CH₂O— and CF₃CH₂O—. Examples of “fluoromethoxy” include CH₂FO—, CHF₂O— and CF₃O—. Examples of “haloalkylthio” include CCl₃S—, CF₃S—, CCl₃CH₂S— and ClCH₂CH₂CH₂S—. Examples of “haloalkylsulfinyl” include CF₃S(O)—, CCl₃S(O)—, CF₃CH₂S(O)— and CF₃CF₂S(O)—. Examples of “haloalkylsulfonyl” include CF₃S(O)₂—, CCl₃S(O)₂—, CF₃CH₂S(O)₂— and CF₃CF₂S(O)₂—.

The total number of carbon atoms in a substituent group is indicated by the “C_(i)-C_(j)” prefix where i and j are numbers from 1 to 12. For example, C₁-C₄ alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C₂ alkoxyalkyl designates CH₃OCH₂—; C₃ alkoxyalkyl designates, for example, CH₃CH(OCH₃)—, CH₃OCH₂CH₂— or CH₃CH₂OCH₂—; and C₄ alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH₃CH₂CH₂OCH₂— and CH₃CH₂OCH₂CH₂—.

As used herein, the following definitions shall apply unless otherwise indicated. The term “optionally substituted” is used interchangeably with the phrase “substituted or unsubstituted” or with the term “(un)substituted.” Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of the other.

The term “unsubstituted” in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term “optionally substituted” means that the number of substituents can be zero. Unless otherwise indicated, optionally substituted groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. The number of optional substituents may be restricted by an expressed limitation. For example, the phrase “optionally substituted with up to 3 substituents selected from R^(9a) on carbon ring members” means that 0, 1, 2 or 3 substituents can be present (if the number of potential connection points allows). Similarly, the phrase “optionally substituted with up to 5 substituents selected from R³ on carbon ring members” means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows. When a range specified for the number of substituents (e.g., r being an integer from 0 to 4 or from 0 to 3 for 5- and 6-membered nitrogen-containing heterocycles in Exhibit A) exceeds the number of positions available for substituents on a ring (e.g., 2 positions available for (R^(a))_(r) on U-27 in Exhibit A), the actual higher end of the range is recognized to be the number of available positions.

When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents, e.g., (R³)_(p) in Table 1 where p is 0, 1, 2, 3, 4 or 5. When a group contains a substituent which can be hydrogen, for example R¹, R⁴, R⁵, R⁶, R⁷ or R¹³, then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a variable group is shown to be optionally attached to a position, for example (R^(a))_(r) in H-23 of Exhibit 1, wherein r may be 0, then hydrogen may be at the position even if not recited in the variable group definition. When one or more positions on a group are said to be “not substituted” or “unsubstituted”, then hydrogen atoms are attached to take up any free valency.

The variables “m”, “n”, “t”, “u”, “v”, “w” and “y” in the Summary of the Invention and corresponding parts of the patent specification relate to subscripts appearing to the right of atoms or other molecular fragments within parentheses and denote the integral number of instances present of the atoms or other molecular fragments within the parentheses. “m” relates to “S(O)_(m)”, “n” relates to “S(O)_(n)”, “t” relates to “—S(═O)_(t)R¹⁰”, “u” and “v” relate to “S(═O)_(u)(═NR¹⁴”, “w” relates to “S(═O)_(w)”, and “y” relates to “S(═O)_(y)R²⁵. For example, “m” being 0, 1 or 2 means that “S(O)_(m)” can be “S”, “S(O)” or “S(O)₂”.

Unless otherwise indicated, a “ring” as a component of Formula 1 is carbocyclic or heterocyclic. The term “ring system” as a component of Formula 1 denotes two fused rings (e.g., a phenyl ring fused to a pyridinyl ring to form quinolinyl). The term “ring member” refers to an atom or other moiety (e.g., O, S(O), S(O)₂ or S(═O)_(u)(═NR¹⁴)_(v)) forming the backbone of a ring or ring system.

The term “carbocyclic ring” denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. Unless otherwise indicated, a carbocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. “Saturated carbocyclic” refers to a ring having a backbone consisting of carbon atoms linked to one another by single bonds; unless otherwise specified, the remaining carbon valences are occupied by hydrogen atoms.

The terms “heterocyclic ring” or “heterocycle” denote a ring or ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur. Typically a heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated, or fully unsaturated ring. The term “saturated heterocyclic ring” refers to a heterocyclic ring containing only single bonds between ring members. In regards to degree of saturation, “a partially unsaturated heterocyclic ring” is intermediate between a saturated heterocyclic ring and a fully unsaturated heterocyclic ring (which may be aromatic). Therefore, as referred to in the present disclosure and claims, the term “partially unsaturated heterocyclic ring” denotes a heterocyclic ring comprising at least one ring member bonded to an adjacent ring member through a double bond and which conceptually potentially accommodates a number of non-cumulated double bonds between adjacent ring members (i.e. in its fully unsaturated counterpart form) greater than the number of double bonds present (i.e. in its partially unsaturated form). When a fully unsaturated heterocyclic ring satisfies Hickel's rule, then said ring is also called a “heteroaromatic ring” or “aromatic heterocyclic ring”. The terms “heteroaromatic ring system” and “heteroaromatic bicyclic ring system” denote a ring system in which at least one atom forming the ring backbone is not carbon, e.g., nitrogen, oxygen or sulfur, and at least one ring is aromatic. Unless otherwise indicated, heterocyclic rings and ring systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.

“Aromatic” indicates that each of the ring atoms is essentially in the same plane and has a p-orbital perpendicular to the ring plane, and that (4n+2) it electrons, where n is a positive integer, are associated with the ring to comply with Huickel's rule. The term “aromatic heterocyclic ring system” denotes a heterocyclic ring system in which at least one ring of the ring system is aromatic. The term “nonaromatic ring system” denotes a carbocyclic or heterocyclic ring system that may be fully saturated, as well as partially or fully unsaturated, provided that none of the rings in the ring system are aromatic. The term “four- to seven-membered nonaromatic heterocyclic ring” refers to rings containing four to seven ring members and which do not satisfy Hickel's rule. This term (as used where R⁶ and R⁷ are taken together) is not limited by carbon atoms only and can include ring members selected from O, S(O)_(n) and NR¹³.

In the context of the present invention when an instance of Q¹, Q² or R¹ comprises a phenyl or a 6-membered fully unsaturated heterocyclic ring, the ortho, meta and para positions of each ring is relative to the connection of the ring to the remainder of Formula 1.

As noted above, Q¹, Q² and R¹ can be (among others) phenyl optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of the Invention. An example of phenyl optionally substituted with one to five substituents is the ring illustrated as U-57 in Exhibit A, wherein R⁸ is as defined in the Summary of the Invention for R⁸ and q is an integer from 0 to 5.

As noted above, Q¹ is, inter alia, a 5- to 6-membered fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(═O) and C(═S), the sulfur atom ring members are independently selected from S(═O)_(u)(═NR¹⁴)_(v), each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q¹ (e.g., a Q¹ ring or ring system is optionally substituted with R³ on carbon ring members and cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₁-C₆ alkoxy, C₂-C₆ alkoxyalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylaminoalkyl and C₃-C₆ dialkylaminoalkyl on nitrogen atom ring members). Similarly, Q² is, inter alia, a 5- to 6-membered saturated, partially unsaturated or fully unsaturated heterocyclic ring or an 8- to 10-membered heteroaromatic bicyclic ring system, each ring or ring system containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, wherein up to 3 carbon atom ring members are independently selected from C(═O) and C(═S), the sulfur atom ring members are independently selected from S(═O)_(u)(═NR¹⁴)_(v), each ring or ring system optionally substituted with up to 5 substituents independently selected from any substituent defined in the Summary of the Invention for Q². As the substituents on the ring or ring system of Q¹ or Q² are optional, 0 to 5 substituents may be present, limited only by the number of available points of attachment. In these definitions of heterocyclic ring and heteroaromatic ring system, the ring members selected from up to 2 O, up to 2 S and up to 4 N atoms are optional, provided at least one ring member is not carbon (e.g., N, O or S). The definition of S(═O)_(u)(═NR¹⁴)_(v) allows the up to 2 sulfur ring members, to be oxidized sulfur moieties (e.g., S(═O) or S(═O)₂) or unoxidized sulfur atoms (i.e. when u and v are both zero). The nitrogen atom ring members may be oxidized as N-oxides, because compounds relating to Formula 1 also include N-oxide derivatives. The up to 3 carbon atom ring members selected from C(═O) and C(═S) are in addition to the up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N atoms.

Also as noted above, R¹ can be (among others) 5- or 6-membered nitrogen-containing aromatic heterocycle, which may be optionally substituted with one or more substituents selected from a group of substituents as defined in the Summary of Invention.

When R¹ is phenyl or a 5- or 6-membered nitrogen-containing aromatic heterocycle, it may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described. Likewise, the ring or ring system of Q¹ or Q² may be attached to the remainder of Formula 1 through any available carbon or nitrogen ring atom, unless otherwise described.

Examples of a 5- to 6-membered fully unsaturated heterocyclic ring include the rings H-1 through H-39 illustrated in Exhibit 1, and examples of an 8- to 10-membered heteroaromatic bicyclic ring system include the ring systems B-1 through B-39 illustrated in Exhibit 2. In Exhibits 1 and 2 the variable R^(a) is any substituent as defined in the Summary of the Invention for Q¹, Q² or R¹ (e.g., a Q¹ ring or ring system is optionally substituted with R³ on carbon ring members and cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₁-C₆ alkoxy, C₂-C₆ alkoxyalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylaminoalkyl and C₃-C₆ dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5 for Q¹ and Q² or from 0 to 3 for R¹, limited by the number of available positions on each depicted ring or ring system.

Exhibit 1

Exhibit 2

Examples of a saturated or partially unsaturated 5- to 6-membered fully unsaturated heterocyclic ring include the rings P-1 through P-40 illustrated in Exhibit 3. In Exhibit 3 the variable R^(a) is any substituent as defined in the Summary of the Invention for Q² (e.g., a Q² ring is optionally substituted with R³ on carbon ring members and cyano, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₁-C₆ alkoxy, C₂-C₆ alkoxyalkyl, C₂-C₆ alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylaminoalkyl and C₃-C₆ dialkylaminoalkyl on nitrogen atom ring members) and r is an integer from 0 to 5, limited by the number of available positions on each depicted ring or ring system.

Exhibit 3

Examples of a 5- or 6-membered nitrogen-containing heterocycle optionally substituted with from one or more substituents of particular note for Q¹, Q² and R¹ include the rings U-1 through U-56 illustrated in Exhibit A wherein R^(a) is any substituent as defined in the Summary of the Invention for Q¹ Q² and R¹, respectively (i.e. for Q¹ and Q²: R³ on carbon atom ring members, and the recited list of possible substituents on nitrogen atom ring members; and for R¹, R^(9a) on carbon ring members and R^(9b) on nitrogen ring members) and r is an integer ranging from 0 to 4 for Q¹ and Q² and from 0 to 3 for R¹, limited by the number of available positions on each U group. Note that some U groups can only be substituted with less than 4 R^(a) groups (e.g., U-4 through U-43 and U-47 through U-56). As U-24, U-25, U-31, U-32, U-33, U-34, U-35, U-36, U-37 and U-38 have only one available position, for these U groups, r is limited to the integers 0 or 1, and r being 0 means that the U group is unsubstituted and a hydrogen is present at the position indicated by (R^(a))_(r).

Exhibit A

Although R^(a) groups are shown in the structures H-1 through H-39, B-1 through B-39, P-1 through P-40, and U-1 through U-57 in Exhibits 1 through 3 and Exhibit A, it is noted that they do not need to be present since they are optional substituents. The nitrogen atoms that require substitution to fill their valence are substituted with H or R^(a). Note that when the attachment point between (R^(a))_(r) and the H, B, P or U group in Exhibits 1 through 3 and Exhibit A is illustrated as floating, (R^(a))_(r) can be attached to any available carbon atom or nitrogen atom of the H, B, P or U group. Note that when the attachment point on the H, B or P group in Exhibits 1 through 3 is illustrated as floating, the H, B or P group can be attached to the remainder of Formula 1 through any available carbon or nitrogen of the H, B or P group by replacement of a hydrogen atom. Of note are alternative depictions of the chemical structures shown in Exhibits 1 through 3 and Exhibit A in which the “R^(a)” variable substituent is replaced by “R^(v)”, wherein the “v” superscript in “R^(v)” does not refer to the subscript variable “v” defined in the Summary of the Invention but instead differentiates “R^(v)” from other substituent variables beginning with “R”.

Examples of where R⁶ and R⁷ are taken together to form a four- to seven-membered nonaromatic heterocyclic ring include the rings G-1 through G-28 as illustrated in Exhibit 4. Note that when R⁶ and R⁷ are taken together to form a ring comprising a ring selected from G-25 through G-28, G² is selected from O, S(O)_(n) or NR¹³. Note that when G² is N, the nitrogen atom can complete its valence by substitution with either H or the substituents corresponding to R¹³ as defined in the Summary of Invention.

Exhibit 4

A wide variety of synthetic methods are known in the art to enable preparation of aromatic and nonaromatic heterocyclic rings and ring systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Press, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.

Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers or as an optically active form.

One skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form N-oxides. One skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of N-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.

One skilled in the art recognizes that some of the compounds disclosed herein can exist in equilibrium with one or more of their respective tautomeric counterparts. Unless otherwise indicated, reference to a compound by one tautomer description is to be considered to include all tautomers. For example, reference to the tautomeric form depicted by Formula 2¹ also includes the tautomic form depicted by Formula 2².

One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.

Compounds selected from Formula 1, geometric and stereoisomers, tautomers, N-oxides, and salts thereof, typically exist in more than one form, and Formula 1 thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term “polymorph” refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.

Embodiments of the present invention as described in the Summary of the Invention include (where Formula 1 as used in the following Embodiments includes N-oxides and salts, geometric isomers, stereoisomers and atropisomers thereof):

Embodiment 1

A compound of Formula 1 wherein X is O, S(O)_(m), NR⁴, CR¹⁵R¹⁶ or C(═O).

Embodiment 2

A compound of Formula 1 wherein X is O, S(O)_(m), NR⁴ or CR¹⁵R¹⁶.

Embodiment 3

A compound of Formula 1 wherein X is O, NR⁴, CR¹⁵R¹⁶ or C(═O).

Embodiment 4

A compound of Formula 1 wherein X is O, NR⁴ or CR¹⁵R¹⁶.

Embodiment 5

A compound of Formula 1 wherein X is O, S(O)_(m) or NR⁴.

Embodiment 6

A compound of Formula 1 wherein X is O or S(O)_(m).

Embodiment 7

A compound of Formula 1 wherein X is O.

Embodiment 8

A compound of Formula 1 wherein X is NR⁴.

Embodiment 9

A compound of Formula 1 wherein X is O or NR⁴.

Embodiment 10

A compound of Formula 1 wherein X is CR¹⁵R¹⁶, C(═O) or C(═S).

Embodiment 11

A compound of Formula 1 or any one of Embodiments 1 through 10 wherein when Q¹ is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R³ substituent is located at a meta position (relative to the connection of the Q¹ ring to the remainder of Formula 1), then said R³ substituent is selected from F, Cl, Br and cyano (—CN).

Embodiment 11a

A compound of Formula 1 or any one of Embodiments 1 through 11 wherein when Q¹ is a six-membered ring and an R³ substituent is located at a meta position (relative to the connection of the Q¹ ring to the remainder of Formula 1), then said R³ substituent is F.

Embodiment 12

A compound of Formula 1 or any one of Embodiments 1 through 11a wherein when Q¹ is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R³ substituent, then said R³ substituent is attached at an ortho position (relative to the connection of the Q¹ ring to the remainder of Formula 1).

Embodiment 13

A compound of Formula 1 or any one of Embodiments 1 through 12 wherein Q¹ is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R³.

Embodiment 14

A compound of Embodiment 13 wherein Q¹ is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R³.

Embodiment 15

A compound of Embodiment 14 wherein Q¹ is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R³.

Embodiment 16

A compound of Embodiment 15 wherein Q¹ is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 17

A compound of Embodiment 16 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q¹ ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q¹.

Embodiment 18

A compound of Embodiment 16 or 17 wherein Q¹ is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 19

A compound of Embodiment 18 wherein Q¹ is phenyl or pyridinyl, each substituted with 2 or 3 substituents independently selected from R³.

Embodiment 20

A compound of Embodiment 19 wherein Q¹ is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R³; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R³; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R³.

Embodiment 21

A compound of Embodiment 20 wherein Q¹ is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R³; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R³.

Embodiment 22

A compound of Embodiment 21 wherein Q¹ is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R³.

Embodiment 23

A compound of Embodiment 21 wherein Q¹ is phenyl substituted at the 2- and 4-positions with substituents independently selected from R³.

Embodiment 24

A compound of Embodiment 21 wherein Q¹ is phenyl substituted at the 2- and 6-positions with substituents independently selected from R³.

Embodiment 25

A compound of Embodiment 18 wherein Q¹ is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 26

A compound of Embodiment 25 wherein Q¹ is pyridinyl substituted with 1 or 2 substituents independently selected from R³.

Embodiment 27

A compound of Embodiment 26 wherein Q¹ is pyridinyl substituted with 1 substituent independently selected from R³.

Embodiment 28

A compound of Formula 1 or any one of Embodiments 1 through 27 wherein when Q² is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) and an R³ substituent is located at a meta position (relative to the connection of the Q² ring to the remainder of Formula 1), then said R³ substituent is selected from F, Cl, Br and cyano (—CN).

Embodiment 29

A compound of Formula 1 or any one of Embodiments 1 through 28 wherein when Q² is a six-membered ring and an R³ substituent is located at a meta position (relative to the connection of the Q² ring to the remainder of Formula 1), then said R³ substituent is F.

Embodiment 30

A compound of Formula 1 or any one of Embodiments 1 through 29 wherein when Q² is a six-membered ring (e.g., phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl) substituted with only one R³ substituent, then said R³ substituent is attached at an ortho position (relative to the connection of the Q² ring to the remainder of Formula 1).

Embodiment 31

A compound of Formula 1 or any one of Embodiments 1 through 30 wherein Q² is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, naphthalenyl, quinolinyl, isoquinolinyl or quinoxalinyl, each optionally substituted with up to 5 substituents independently selected from R³.

Embodiment 32

A compound of Embodiment 31 wherein Q² is phenyl, thienyl, pyridinyl, pyridazinyl, pyrazinyl or pyrimidinyl, each optionally substituted with up to 5 substituents independently selected from R³.

Embodiment 33

A compound of Embodiment 32 wherein Q² is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with from 1 to 4 substituents independently selected from R³.

Embodiment 34

A compound of any one of Embodiments 31 through 33 wherein Q² is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl, each substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 35

A compound of Embodiment 34 wherein the substituents are located at the ortho and/or para positions (relative to the connection of the Q² ring to the remainder of Formula 1) of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q².

Embodiment 36

A compound of any one of Embodiments 34 or 35 wherein Q² is phenyl or pyridinyl, each substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 37

A compound of Embodiment 36 wherein Q² is phenyl substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 38

A compound of Embodiment 37 wherein Q² is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R³; or phenyl substituted at the 2- and 4-positions with substituents independently selected from R³; or phenyl substituted at the 2- and 6-positions with substituents independently selected from R³.

Embodiment 39

A compound of Embodiment 38 wherein Q² is phenyl substituted at the 2-, 4- and 6-positions with substituents independently selected from R³.

Embodiment 40

A compound of Embodiment 38 wherein Q² is phenyl substituted at the 2- and 4-positions with substituents independently selected from R³.

Embodiment 41

A compound of Embodiment 38 wherein Q² is phenyl substituted at the 2- and 6-positions with substituents independently selected from R³.

Embodiment 42

A compound of Embodiment 36 wherein Q² is pyridinyl substituted with 1, 2 or 3 substituents independently selected from R³.

Embodiment 43

A compound of Embodiment 42 wherein Q² is pyridinyl substituted with 1 or 2 substituents independently selected from R³.

Embodiment 44

A compound of Embodiment 43 wherein Q² is pyridinyl substituted with 1 substituent selected from R³.

Embodiment 45

A compound of Formula 1 or any one of Embodiments 1 through 44 wherein at least one of Q¹ and Q² is phenyl optionally substituted with R³ (e.g., optionally substituted with up to 5 substituents independently selected from R³).

Embodiment 46

A compound of Embodiment 45 wherein at least one of Q¹ and Q² is phenyl substituted with 2, 3 or 4 substituents independently selected from R³.

Embodiment 47

A compound of Embodiment 46 wherein at least one Q¹ and Q² is phenyl substituted with 2 or 3 substituents independently selected from R³.

Embodiment 48

A compound of Embodiment 47 wherein each of Q¹ and Q² is phenyl substituted with 2 or 3 substituents independently selected from R³.

Embodiment 49

A compound of Formula 1 or any one of Embodiments 1 through 48 wherein R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, CO₂R⁵, C(O)NR⁶R⁷, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl; or R¹ is a five- or six-membered nitrogen-containing aromatic heterocycle optionally substituted with up to 3 substituents independently selected from R^(9a) on carbon atom ring members and R^(9b) on nitrogen atom ring members.

Embodiment 50

A compound of Embodiment 49 wherein R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, cyano, C₁-C₆ alkoxy or C₁-C₆ haloalkoxy; or R¹ is pyridinyl, pyrimidinyl, pyrazolyl or oxazolyl, each optionally substituted with up to 3 substituents independently selected from R^(9a) on carbon atom ring members and R^(9b) on nitrogen atom ring members.

Embodiment 51

A compound of Embodiment 50 wherein R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, CO₂R⁵, C(O)NR⁶R⁷, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl.

Embodiment 52

A compound of Embodiment 51 wherein R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C(O)NR⁶R⁷, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl.

Embodiment 53

A compound of Embodiment 52 wherein R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl.

Embodiment 54

A compound of Embodiment 53 wherein R¹ is H, halogen or C₁-C₆ alkyl.

Embodiment 55

A compound of Embodiment 54 wherein R¹ is H or CH₃.

Embodiment 56

A compound of Embodiment 55 wherein R¹ is H.

Embodiment 57

A compound of Formula 1 or any one of Embodiments 1 through 56 wherein R¹ is other than an optionally substituted phenyl or an optionally substituted five- or six-membered nitrogen-containing aromatic heterocycle.

Embodiment 58

A compound of Formula 1 or any one of Embodiments 1 through 50 wherein R¹ is other than H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₃-C₇ cycloalkyl, CO₂R⁵, C(O)NR⁶R⁷, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl.

Embodiment 59

A compound of Formula 1 or any one of Embodiments 1 through 58 wherein R^(1a) is H.

Embodiment 60

A compound of Formula 1 or any one of Embodiments 1 through 59 wherein R² is CH₃, CH₂CH₃, halogen, cyano, cyanomethyl, monohalomethyl, hydroxymethyl, methoxy or methylthio; or cyclopropyl optionally substituted with up to 2 substituents independently selected from halogen and methyl.

Embodiment 61

A compound of Embodiment 60 wherein R² is CH₃, CH₂CH₃, Cl, Br or I.

Embodiment 62

A compound of Embodiment 61 wherein R² is CH₃, CH₂CH₃, Cl or Br.

Embodiment 63

A compound of Embodiment 62 wherein R² is CH₃, Cl or Br.

Embodiment 64

A compound of Embodiment 63 wherein R² is CH₃ or Cl.

Embodiment 65

A compound of Embodiment 64 wherein R² is CH₃.

Embodiment 66

A compound of Embodiment 62 wherein R² is Cl or Br.

Embodiment 67

A compound of Embodiment 66 wherein R² is Cl.

Embodiment 68

A compound of Formula 1 or any one of Embodiments 1 through 67 wherein R⁵ is H or C₁-C₆ alkyl.

Embodiment 69

A compound of Embodiment 68 wherein R⁵ is H, CH₃ or CH₂CH₃.

Embodiment 70

A compound of Embodiment 68 wherein R⁵ is C₁-C₆ alkyl.

Embodiment 71

A compound of Embodiment 69 or 70 wherein R⁵ is CH₃ or CH₂CH₃.

Embodiment 72

A compound of Formula 1 or any one of Embodiments 1 through 71 wherein when R⁶ is separate (i.e. not taken together with R⁷ to form a ring), then R⁶ is H or C₁-C₆ alkyl.

Embodiment 73

A compound of Embodiment 72 wherein R⁶ is H.

Embodiment 74

A compound of Formula 1 or any one of Embodiments 1 through 73 wherein when R⁷ is separate (i.e. not taken together with R⁶ to form a ring), then R⁷ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl or C₄-C₈ alkylcycloalkyl.

Embodiment 75

A compound of Embodiment 74 wherein R⁷ is H or C₁-C₆ alkyl.

Embodiment 76

A compound of Embodiment 75 wherein R⁷ is H.

Embodiment 77

A compound of Formula 1 or any one Embodiments 1 through 76 wherein when R⁶ and R⁷ are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring contains ring members, in addition to the connecting nitrogen atom, selected from carbon atoms and up to one ring member selected from O and NR¹³.

Embodiment 78

A compound of Embodiment 77 wherein when R⁶ and R⁷ are taken together with the nitrogen atom to which they are connected to form a nonaromatic heterocyclic ring, the ring is six-membered and contains one ring member selected from O and NR¹³ in addition to the connecting nitrogen atom and ring members selected from carbon atoms.

Embodiment 79

A compound of Embodiment 77 wherein R⁶ and R⁷ are taken together with the nitrogen atom to which they are connected to form a piperidine ring.

Embodiment 80

A compound of Embodiment 78 wherein R⁶ and R⁷ are taken together with the nitrogen atom to which they are connected to form a piperazine or morpholine ring.

Embodiment 81

A compound of Formula 1 or any one of Embodiments 1 through 80 wherein each R⁸ is independently selected from halogen, C₁-C₂ alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy, C₁-C₂ haloalkoxy, cyano and nitro.

Embodiment 82

A compound of Embodiment 81 wherein each R⁸ is independently selected from halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, cyano and nitro.

Embodiment 83

A compound of Embodiment 82 wherein each R⁸ is independently Cl or F.

Embodiment 84

A compound of Formula 1 or any one of Embodiments 1 through 83 wherein each R^(9a) is independently selected from halogen, C₁-C₂ alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy, C₁-C₂ haloalkoxy, cyano and nitro.

Embodiment 85

A compound of Embodiment 84 wherein each R^(9a) is independently selected from halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, cyano and nitro.

Embodiment 86

A compound of Embodiment 85 wherein each R^(9a) is independently selected from Cl, F, CH₃, —OCH₃ and cyano.

Embodiment 87

A compound of Embodiment 86 wherein each R^(9a) is independently Cl or F.

Embodiment 88

A compound of Formula 1 or any one of Embodiments 1 through 87 wherein each R^(9b) is independently C₁-C₂ alkyl.

Embodiment 89

A compound of Formula 1 or any one of Embodiments 1 through 88 wherein each R³ is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₃ alkylsulfinyl, C₁-C₃ haloalkylsulfinyl, C₁-C₃ alkylsulfonyl, C₁-C₃ haloalkylsulfonyl, C₃-C₄ cycloalkyl, C(═S)NH₂ and —U—V-T.

Embodiment 90

A compound of Embodiment 89 wherein each R³ is independently selected from halogen, cyano, nitro, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy and —U—V-T.

Embodiment 91

A compound of Embodiment 90 wherein each R³ is independently selected from F, Cl, Br, cyano, nitro, CH₃, CF₃, —OCH₃, —OCHF₂ and —U—V-T.

Embodiment 92

A compound of Formula 1 or any one of Embodiments 1 through 91 wherein at least one R³ substituent on the ring or ring system of Q¹ or Q² is —U—V-T.

Embodiment 93

A compound of Formula 1 or any one of Embodiments 1 through 91 wherein each R³ is other than —U—V-T.

Embodiment 94

A compound of Embodiment 89 wherein each R³ is independently selected from halogen, cyano, nitro, amino, methylamino, dimethylamino, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, C₁-C₃ alkylsulfinyl, C₁-C₃ haloalkylsulfinyl, C₁-C₃ alkylsulfonyl, C₁-C₃ haloalkylsulfonyl and C₃-C₄ cycloalkyl.

Embodiment 95

A compound of Embodiment 94 wherein each R³ is independently selected from halogen, cyano, nitro, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy and C₁-C₃ haloalkoxy.

Embodiment 96

A compound of Embodiment 95 wherein each R³ is independently selected from halogen, cyano, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy and C₁-C₃ haloalkoxy.

Embodiment 97

A compound of Embodiment 96 wherein each R³ is independently selected from F, Cl, Br, cyano, C₁-C₂ alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy.

Embodiment 98

A compound of Embodiment 97 wherein each R³ is independently selected from F, Cl, Br, cyano, methyl, C₁-C₂ alkoxy and fluoromethoxy.

Embodiment 99

A compound of Embodiment 98 wherein each R³ is independently selected from F, Cl, cyano, methyl, C₁-C₂ alkoxy and fluoromethoxy.

Embodiment 100

A compound of Embodiment 95 wherein each R³ is independently selected from F, Cl, Br, cyano, nitro, CH₃, CF₃, —OCH₃ and —OCHF₂.

Embodiment 101

A compound of any one of Embodiments 89 through 98 or 100 wherein each R³ is independently selected from F, Cl, Br, cyano and methoxy.

Embodiment 102

A compound of Embodiment 101 wherein each R³ is independently selected from F, Cl, Br and cyano.

Embodiment 103

A compound of Embodiment 101 wherein each R³ is independently selected from F, Cl, cyano and —OCH₃.

Embodiment 104

A compound of Formula 1 or any one of Embodiments 1 through 92 wherein each U is independently O or NR²².

Embodiment 105

A compound of Embodiment 104 wherein each U is independently O or NH.

Embodiment 106

A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 105 wherein each V is C₂-C₄ alkylene.

Embodiment 107

A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 106 wherein each T is independently NR^(23a)R^(23b) or OR²⁴.

Embodiment 108

A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 107 wherein each R^(23a) and R^(23b) is independently H, C₁-C₆ alkyl or C₁-C₆ haloalkyl.

Embodiment 109

A compound of Formula 1 or any one of Embodiments 1 through 92 and 104 through 108 wherein each R²⁴ is independently H, C₁-C₆ alkyl or C₁-C₆ haloalkyl.

Embodiment 110

A compound of Formula 1 or any one of Embodiments 1 through 109 wherein when an R³ substituent attached to phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl of Q¹ or Q² is other than F, Cl, Br, cyano, methyl, C₁-C₂ alkoxy and fluoromethoxy, then said R³ substituent is attached at the para position (of the phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl ring).

Embodiment 111

A compound of Formula 1 or any one of Embodiments 1 through 110 wherein R⁴ is H, formyl, C₃-C₇ cycloalkyl or —SR¹⁰; or C₁-C₆ alkyl or C₁-C₆ haloalkyl, each optionally substituted with up to 2 R¹².

Embodiment 112

A compound of Embodiment 111 wherein R⁴ is H, formyl, C₃-C₇ cycloalkyl or —SR¹⁰; or C₁-C₆ alkyl substituted with one R¹².

Embodiment 113

A compound of Embodiment 112 wherein R⁴ is H, formyl, —CH₂OCH₃, cyclopropyl, —SCH₃, —SCF₃ or —CH₂CN.

Embodiment 114

A compound of Embodiment 113 wherein R⁴ is H, formyl, cyclopropyl or —CH₂CN.

Embodiment 115

A compound of Embodiment 113 wherein R⁴ is H, formyl, —CH₂OCH₃, cyclopropyl, —SCH₃ or —SCF₃.

Embodiment 116

A compound of Embodiment 115 wherein R⁴ is H, formyl or cyclopropyl.

Embodiment 117

A compound of Embodiment 114 or 116 wherein R⁴ is H.

Embodiment 118

A compound of Formula 1 or any one of Embodiments 1 through 117 wherein R¹³ is H or CH₃.

Embodiment 119

A compound of Embodiment 118 wherein R¹³ is CH₃.

Embodiment 120

A compound of Formula 1 or any one of Embodiments 1 through 119 wherein each R¹² is independently C₃-C₇ cycloalkyl, C₁-C₄ alkoxy or cyano.

Embodiment 121

A compound of Embodiment 120 wherein each R¹² is independently cyclopropyl, —OCH₃ or cyano.

Embodiment 122

A compound of Embodiment 120 wherein each R¹² is independently C₃-C₇ cycloalkyl or C₁-C₄ alkoxy.

Embodiment 123

A compound of Embodiment 122 wherein each R¹² is independently cyclopropyl or —OCH₃.

Embodiment 124

A compound of Formula 1 or any one of Embodiments 1 through 123 wherein R¹⁰ is CH₃, CH₂CH₃, CF₃ or CF₂CF₃.

Embodiment 125

A compound of Embodiment 124 wherein R¹⁰ is CH₃.

Embodiment 126

A compound of Formula 1 or any one of Embodiments 1 through 125 wherein R¹¹ is C₁-C₆ alkyl, C₁-C₆ alkoxy or C₁-C₆ alkylthio.

Embodiment 127

A compound of Embodiment 126 wherein R¹¹ is CH₃, CH₂CH₃, —OCH₃, —OCH₂CH₃, —SCH₃ or —SCH₂CH₃.

Embodiment 128

A compound of Embodiment 127 wherein R¹¹ is CH₃, —OCH₃ or —SCH₃.

Embodiment 129

A compound of Formula 1 or any one of Embodiments 1 through 128 wherein R¹⁵ is H or CH₃.

Embodiment 130

A compound of Embodiment 129 wherein R¹⁵ is H.

Embodiment 131

A compound of Formula 1 or any one of Embodiments 1 through 130 wherein R¹⁶ is CH₃ or OR¹⁸.

Embodiment 132

A compound of Embodiment 131 wherein R¹⁶ is OR¹⁸.

Embodiment 133

A compound of Formula 1 or any one of Embodiments 1 through 132 wherein R¹⁸ is H.

Embodiment 134

A compound of Formula 1 or any one of Embodiments 1 through 133 wherein W is O.

Embodiment 135

A compound of Formula 1 or any one of Embodiments 1 through 134 wherein M⁺ is a cation selected from sodium, potassium and lithium ions.

Embodiment 136

A compound of Embodiment 135 wherein M⁺ is a cation selected from sodium and potassium ions.

Embodiment 137

A compound of Embodiment 136 wherein M⁺ is a sodium ion.

Embodiment 138

A compound of Formula 1 or any one of Embodiments 1 through 137 wherein m is 0.

Embodiment 139

A compound of Formula 1 or any one of Embodiments 1 through 138 wherein n is 0.

Embodiments of this invention, including Embodiments 1-139 above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and intermediate compounds (e.g. compounds of Formula 2) useful for preparing the compounds of Formula 1. In addition, embodiments of this invention, including Embodiments 1-139 above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present invention.

Combinations of Embodiments 1-139 are illustrated by:

Embodiment A

A compound of Formula 1 wherein

-   -   Q¹ is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl,         each substituted with from 1 to 4 substituents independently         selected from R³; provided that when an R³ substituent is         located at a meta position, then said R³ substituent is selected         from F, Cl, Br and cyano;     -   Q² is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl,         each substituted with 1, 2 or 3 substituents independently         selected from R³, provided that when an R³ substituent is         located at a meta position, then said R³ substituent is selected         from F, Cl, Br and cyano;     -   X is O, NR⁴, C(═O) or CR¹⁵R¹⁶;     -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, CO₂R⁵,         C(O)NR⁶R⁷, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅         alkoxyalkyl;     -   R^(1a) is H;     -   R² is CH₃, CH₂CH₃, Cl or Br;     -   each R³ is independently selected from halogen, cyano, nitro,         amino, methylamino, dimethylamino, C₁-C₄ alkyl, C₁-C₄ haloalkyl,         C₁-C₃ alkoxy, C₁-C₃ haloalkoxy C₁-C₃ alkylthio, C₁-C₃         haloalkylthio, C₁-C₃ alkylsulfinyl, C₁-C₃ haloalkylsulfinyl,         C₁-C₃ alkylsulfonyl, C₁-C₃ haloalkylsulfonyl, C₃-C₄ cycloalkyl,         C(═S)NH₂ and —U—V-T;     -   R⁴ is H, formyl, C₃-C₇ cycloalkyl or —SR¹⁰; or C₁-C₆ alkyl or         C₁-C₆ haloalkyl, each optionally substituted with up to 2 R¹²;     -   R⁵ is C₁-C₆ alkyl;     -   R⁶ is H or C₁-C₆ alkyl;     -   R⁷ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl or C₄-C₈ alkylcycloalkyl;         or     -   R⁶ and R⁷ are taken together with the nitrogen atom to which         they are connected to form a four- to seven-membered nonaromatic         heterocyclic ring containing ring members, in addition to the         connecting nitrogen atom, selected from carbon atoms and up to         one ring member selected from O and NR¹³;     -   each R¹² is independently C₃-C₇ cycloalkyl, C₁-C₄ alkoxy or         cyano;     -   R¹³ is H or CH₃;     -   R¹⁵ is H or CH₃; and     -   R¹⁶ is OR¹⁸.

Embodiment B

A compound of Embodiment A wherein

-   -   Q¹ is phenyl or pyridinyl, each substituted with 1, 2 or 3         substituents independently selected from R³;     -   Q² is phenyl or pyridinyl, each substituted with 1, 2 or 3         substituents independently selected from R³;     -   R¹ is H, halogen or C₁-C₆ alkyl;     -   R² is CH₃, Cl or Br;     -   each R³ is independently selected from halogen, cyano, nitro,         C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy and         —U—V-T;     -   R⁴ is H, formyl, C₃-C₇ cycloalkyl or —SR¹⁰; or C₁-C₆ alkyl         substituted with one R¹²;     -   each R¹² is independently cyclopropyl, —OCH₃ or cyano;     -   R¹⁵ is H;     -   each U is independently O or NH;     -   each V is C₂-C₄ alkylene;     -   each T is independently NR^(23a)R^(23b) or OR²⁴;     -   each R^(23a) and R^(23b) is independently H, C₁-C₆ alkyl or         C₁-C₆ haloalkyl; and     -   each R²⁴ is independently H, C₁-C₆ alkyl or C₁-C₆ haloalkyl.

Embodiment C

A compound of Embodiment B wherein

-   -   at least one of Q¹ and Q² is phenyl substituted with 2 or 3         substituents independently selected from R³;     -   R¹ is H or CH₃;     -   R² is CH₃;     -   R⁴ is H;     -   each R³ is independently selected from halogen, cyano, C₁-C₃         alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy and C₁-C₃ haloalkoxy; and     -   R¹⁸ is H.

Embodiment D

A compound of Embodiment C wherein

-   -   Q¹ is phenyl substituted at the 2-, 4- and 6-positions with         substituents independently selected from R³; or phenyl         substituted at the 2- and 4-positions with substituents         independently selected from R³; or phenyl substituted at the 2-         and 6-positions with substituents independently selected from         R³;     -   Q² is phenyl substituted at the 2-, 4- and 6-positions with         substituents independently selected from R³; or phenyl         substituted at the 2- and 4-positions with substituents         independently selected from R³; or phenyl substituted at the 2-         and 6-positions with substituents independently selected from         R³;     -   X is O, NR⁴ or CR¹⁵R¹⁶;     -   R¹ is H;     -   each R³ is independently selected from F, Cl, Br, cyano, C₁-C₂         alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy and C₁-C₂ haloalkoxy; and     -   R⁴ is H.

Embodiment E

A compound of Embodiment D wherein

-   -   each R³ is independently selected from F, Cl, Br, cyano, methyl,         C₁-C₂ alkoxy and fluoromethoxy.

Embodiment F

A compound of Embodiment E wherein

-   -   X is O or NH; and     -   each R³ is independently selected from F, Cl, Br, cyano and         methoxy.

Specific embodiments include compounds of Formula 1 selected from the group consisting of:

-   4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine     (Compound 18), -   N-(4-chlorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 22), -   4-(2,6-difluoro-4-methoxyphenyl)-N-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 23), -   4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine     (Compound 24), -   N-(2,6-difluoro-4-methoxyphenyl)-4-(3,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 36), -   4-(2,4-difluorophenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine     (Compound 41), -   4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile     (Compound 45), -   4-[[4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3-fluorobenzonitrile     (Compound 361), -   4-(2-chloro-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 172), -   4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3-fluorobenzonitrile     (Compound 118), -   3-chloro-4-[[4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile     (Compound 358), -   4-(2-chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol -   (Compound 351), -   N,4-bis(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 175), -   N-(2-chloro-4-fluorophenyl)-4-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 193), -   N-(2-chloro-4,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 297), -   N-(2-chloro-4,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 343), -   N-(4-chloro-2,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 349), -   N-(4-chloro-2,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 357), -   3-chloro-4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile     (Compound 139), -   4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]amino]-3,5-difluorobenzonitrile     (Compound 91), -   4-[[4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-2,5-difluorobenzonitrile     (Compound 148), -   N-(2-chloro-4-fluorophenyl)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 87), -   α,4-bis(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol     (Compound 352), -   N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-amine     (Compound 286), -   N-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 287), -   N-(2,6-dichloro-4-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 368), -   3-chloro-4-[5-[(2-chloro-4,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-benzonitrile     (Compound 332), -   3-chloro-4-[5-[(4-chloro-2,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-benzonitrile     (Compound 336), -   N-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 346), -   4-(2-chloro-4-fluorophenyl)-N-(2,4-dichloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 367), -   4-(2-chloro-4-fluorophenyl)-N-(2,6-dichloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 369), -   4-[[4-(2-bromo-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3-fluorobenzonitrile     (Compound 284), -   N-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 265), -   4-(2-bromo-4-fluorophenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine     (Compound 266), -   N-(4-bromo-2,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 364), -   4-[[4-(2-bromo-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile     (Compound 232), -   4-(2-bromo-4-fluorophenyl)-N-(2-chloro-4,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 292), -   4-(2-bromo-4-fluorophenyl)-N-(4-chloro-2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 360), -   N-(4-bromo-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 365), -   3-bromo-4-[[4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile     (Compound 372), -   3-chloro-4-[[4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]benzonitrile     (Compound 373), -   N-(2,4-dichloro-6-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 374), -   N-(2,6-dichloro-4-fluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 375), -   N-(2-bromo-4,6-difluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 376), -   N-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 377), -   N-(4-bromo-2,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 378), -   N-(2-bromo-4,6-difluorophenyl)-4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 379), -   N-(2-bromo-4,6-difluorophenyl)-4-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine     (Compound 380), -   α-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol     (Compound 381), -   4-[5-[(2-chloro-4,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-3-fluorobenzonitrile     (Compound 382), -   4-[5-[(4-chloro-2,6-difluorophenyl)amino]-1,3-dimethyl-1H-pyrazol-4-yl]-3-fluorobenzonitrile     (Compound 383), -   α-(2-chloro-4,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol     (Compound 384), -   α-(2-bromo-4-fluorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol     (Compound 385), and -   α-(2-bromo-4-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol     (Compound 386).

This invention provides a fungicidal composition comprising a compound of Formula 1 (including all geometric and stereoisomers, N-oxides, and salts thereof), and at least one other fungicide. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.

This invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, N-oxides, and salts thereof), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.

This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, N-oxides, and salts thereof). Of note as embodiment of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments describe above. Of particular note are embodiments where the compounds are applied as compositions of this invention.

Of note are compounds of Formula 1 that are compounds of Formula 1P (including all geometric and stereoisomers), N-oxides, and salts thereof, and also agricultural compositions containing them and their use as fungicides:

wherein

-   -   Q¹ and Q² are independently phenyl, thienyl, pyridinyl,         pyridazinyl, pyrazinyl or pyrimidinyl, each optionally         substituted with up to 5 substituents independently selected         from R³;     -   X is O, S(O)_(m) or NR⁴;     -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₄ alkenyl,         C₂-C₄ alkynyl, C₃-C₇ cycloalkyl, CO₂R⁵, C(O)NR⁶R⁷, cyano, C₁-C₆         alkoxy, C₁-C₆ haloalkoxy or C₂-C₅ alkoxyalkyl; or     -   R¹ is phenyl optionally substituted with up to 3 R⁸; or a five-         or six-membered nitrogen-containing aromatic heterocycle         optionally substituted with up to 3 substituents independently         selected from R^(9a) on carbon atom ring members and R^(9b) on         nitrogen atom ring members;     -   R² is CH₃, CH₂CH₃, cyclopropyl or halogen;     -   each R³ is independently selected from halogen, cyano, nitro,         amino, methylamino, dimethylamino, C₁-C₄ alkyl, C₁-C₄ haloalkyl,         C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃         haloalkylthio, C₁-C₃ alkylsulfinyl, C₁-C₃ haloalkylsulfinyl,         C₁-C₃ alkylsulfonyl, C₁-C₃ haloalkylsulfonyl, C₃-C₄ cycloalkyl,         C₃-C₇ cycloalkoxy, C₄-C₆ alkylcycloalkyl, C₄-C₆ cycloalkylalkyl,         C₃-C₇ halocycloalkyl, C₂-C₄ alkenyl and C₂-C₄ alkynyl;     -   R⁴ is H, formyl, C₃-C₇ cycloalkyl, —SO₃-M⁺, —SR¹⁰ or —(C═W)R¹¹;         or C₁-C₆ alkyl or C₁-C₆ haloalkyl, each optionally substituted         with up to 2 R¹²;     -   R⁵ is H, C₁-C₆ alkyl or C₁-C₆ haloalkyl;     -   R⁶ and R⁷ are independently selected from H, C₁-C₆ alkyl, C₁-C₆         haloalkyl, C₃-C₇ cycloalkyl, C₄-C₈ cycloalkylalkyl and C₄-C₈         alkylcycloalkyl; or     -   R⁶ and R⁷ are taken together with the nitrogen atom to which         they are connected to form a four- to seven-membered nonaromatic         heterocyclic ring containing ring members, in addition to the         connecting ring nitrogen atom, selected from carbon atoms and         optionally up to one ring member selected from O, S(O)_(n) and         NR¹³;     -   each R⁸, R^(9a) and R^(9b) is independently selected from         halogen, C₁-C₂ alkyl, C₁-C₂ haloalkyl, C₁-C₂ alkoxy, C₁-C₂         haloalkoxy, cyano, nitro, SCH₃, S(O)CH₃ and S(O)₂CH₃;     -   R¹⁰ is C₁-C₆ alkyl or C₁-C₆ haloalkyl;     -   R¹¹ is C₁-C₆ alkyl, C₁-C₆ alkoxy, C₂-C₇ alkoxyalkyl, C₂-C₇         alkylaminoalkyl, C₂-C₈ dialkylaminoalkyl, C₁-C₆ alkylthio or         C₂-C₇ alkylthioalkyl;     -   each R¹² is independently C₃-C₇ cycloalkyl, C₁-C₄ alkoxy, C₁-C₄         haloalkoxy, C₁-C₄ alkylthio, C₁-C₄ alkylsulfinyl or C₁-C₄         alkylsulfonyl;     -   R¹³ is H, C₁-C₃ alkyl or C₂-C₃ haloalkyl;     -   W is O or S;     -   M⁺ is a cation;     -   m is 0, 1 or 2; and     -   n is 0, 1 or 2.

Accordingly of note is a compound selected from Formula 1P (including all geometric and stereoisomers), N-oxides, and salts thereof, as defined above. Also of note are counterpart embodiments that are embodiment counterparts to Embodiments 1 through 139 and Embodiments A through F wherein in said counterpart embodiments “Formula 1” is replaced by “Formula 1P” and the scope of said counterpart embodiments does not exceed the scope defined above for Formula 1P. Examples of combinations of Embodiments 1 through 139 as applied to Formula 1P are Embodiments AP, BP, CP, DP and EP:

Embodiment AP

A compound of Formula 1P wherein

-   -   Q¹ is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl,         each substituted with from 1 to 4 substituents independently         selected from R³;     -   Q² is phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl,         each substituted with 1, 2 or 3 substituents independently         selected from R³     -   X is O or NR⁴;     -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, CO₂R⁵,         C(O)NR⁶R⁷, cyano, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy or C₂-C₅         alkoxyalkyl; or     -   R¹ is a five- or six-membered nitrogen-containing aromatic         heterocycle optionally substituted with up to 3 substituents         independently selected from R^(9a) on carbon atom ring members         and R^(9b) on nitrogen atom ring members;     -   R² is CH₃, CH₂CH₃, Cl or Br;     -   each R³ is independently selected from halogen, cyano, nitro,         amino, methylamino, dimethylamino, C₁-C₄ alkyl, C₁-C₄ haloalkyl,         C₁-C₃ alkoxy, C₁-C₃ haloalkoxy C₁-C₃ alkylthio, C₁-C₃         haloalkylthio, C₁-C₃ alkylsulfinyl, C₁-C₃ haloalkylsulfinyl,         C₁-C₃ alkylsulfonyl, C₁-C₃ haloalkylsulfonyl and C₃-C₄         cycloalkyl;     -   R⁴ is H, formyl, C₃-C₇ cycloalkyl or —SR¹⁰; or C₁-C₆ alkyl or         C₁-C₆ haloalkyl, each optionally substituted with up to 2 R¹²;     -   R⁵ is H or C₁-C₆ alkyl;     -   R⁶ is H or C₁-C₆ alkyl;     -   R⁷ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl or C₄-C₈ alkylcycloalkyl;         or     -   R⁶ and R⁷ are taken together with the nitrogen atom to which         they are connected to form a four- to seven-membered nonaromatic         heterocyclic ring containing ring members, in addition to the         connecting nitrogen atom, selected from carbon atoms and up to         one ring member selected from O and NR¹³;     -   each R⁸ is independently selected from halogen, C₁-C₂ alkyl,         C₁-C₂ haloalkyl, C₁-C₂ alkoxy, C₁-C₂ haloalkoxy, cyano and         nitro;     -   each R^(9a) is independently selected from halogen, C₁-C₂ alkyl,         C₁-C₂ haloalkyl, C₁-C₂ alkoxy, C₁-C₂ haloalkoxy, cyano and         nitro;     -   each R^(9b) is C₁-C₂ alkyl;     -   R¹⁰ is CH₃, CH₂CH₃, CF₃ or CF₂CF₃;     -   each R¹² is independently C₃-C₇ cycloalkyl or C₁-C₄ alkoxy; and     -   R¹³ is H or CH₃.

Embodiment BP

A compound of Embodiment AP wherein

-   -   Q¹ is phenyl or pyridinyl, each substituted with 1, 2 or 3         substituents independently selected from R³;     -   Q² is phenyl or pyridinyl, each substituted with 1, 2 or 3         substituents independently selected from R³;     -   X is NR⁴;     -   R¹ is H, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, cyano, C₁-C₆         alkoxy or C₁-C₆ haloalkoxy;     -   R² is CH₃;     -   each R³ is independently selected from halogen, cyano, nitro,         C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy and C₁-C₃ haloalkoxy;     -   R⁴ is H, formyl, C₃-C₇ cycloalkyl or —SR¹⁰; or C₁-C₆ alkyl         substituted with one R¹²;     -   R¹⁰ is CH₃; and     -   each R¹² is independently cyclopropyl or —OCH₃.

Embodiment CP

A compound of Embodiment AP wherein

-   -   Q¹ is phenyl substituted at the 2-, 4- and 6-positions with         substituents independently selected from R³; or     -   Q¹ is phenyl substituted at the 2- and 4-positions with         substituents independently selected from R³;     -   Q² is phenyl substituted at the 2-, 4- and 6-positions with         substituents independently selected from R³;     -   X is O;     -   R² is CH₃;     -   each R³ is independently selected from F, Cl, Br, cyano, nitro,         CH₃, CF₃, —OCH₃, and —OCHF₂; and     -   R⁴ is H, formyl or cyclopropyl.

Embodiment DP

A compound of Embodiment CP wherein

-   -   Q¹ is phenyl substituted at the 2- and 4-positions with         substituents independently selected from R³;     -   Q² is phenyl substituted at the 2-, 4- and 6-positions with         substituents independently selected from R³;     -   each R³ is independently selected from F, Cl, cyano and —OCH₃;         and     -   R⁴ is H.

Embodiment EP

A compound of Embodiment BP wherein

-   -   Q¹ is phenyl substituted at the 2- and 4-positions with         substituents independently selected from R³;     -   Q² is phenyl substituted at the 2-, 4- and 6-positions with         substituents independently selected from R³;     -   each R³ is independently selected from F, Cl, CN and —OCH₃; and     -   R⁴ is H.

Also of note is a fungicidal composition comprising a fungicidally effective amount of a compound of Formula 1P (including all geometric and stereoisomers, N-oxides, and salts thereof) or any one of counterpart embodiments that are embodiment counterparts to Embodiments 1 through 139 and Embodiments A through F (e.g., Embodiment AP, BP, CP, DP or EP), and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Also of note is a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1P (including all geometric and stereoisomers, N-oxides, and salts thereof) or any one of said counterpart embodiments. Of particular note are embodiments where the compounds of Formula 1P are applied as compositions of this invention.

One or more of the following methods and variations as described in Schemes 1-24 can be used to prepare the compounds of Formula 1 (including Formula 1P). The definitions of Q¹, Q², R¹, R² and m in the compounds of Formulae 1-33 below are as defined above in the Summary of the Invention unless otherwise noted. Formulae 1a, 1b, 1c, 1d, 1e, 1f, 1g and 1h are various subsets of Formula 1; Formulae 4a, 4b and 4c are various subsets of Formula 4; Formulae 6a and 6b are various subsets of Formula 6; Formula 11a is a subset of Formula 11; Formula 13a is a subset or analog of Formula 13; and Formula 17a is a subset of Formula 17. Substituents for each subset formula are as defined for its parent formula unless otherwise noted.

As illustrated in Scheme 1, sulfoxides and sulfones of Formula 1b (i.e. Formula 1 wherein X is S(O)_(m) and m is 1 or 2) can be made via oxidation of the linking sulfur atom on sulfides of Formula 1a (i.e. Formula 1 wherein X is S(O)_(m) and m is 0). In this method a compound of Formula 1b wherein m is 1 (i.e. sulfoxides) or m is 2 (i.e. sulfones) is prepared by oxidizing a corresponding sulfide of Formula 1a with a suitable oxidizing agent. In a typical procedure, an oxidizing agent in an amount from 1 to 4 equivalents depending on the oxidation state of the product desired is added to a solution of the compound of Formula 1a in a solvent. Useful oxidizing agents include Oxone® (potassium peroxymonosulfate), hydrogen peroxide, sodium periodate, peracetic acid and 3-chloroperbenzoic acid. The solvent is selected with regard to the oxidizing agent employed. Aqueous ethanol or aqueous acetone is preferably used with potassium peroxymonosulfate, and dichloromethane is generally preferable with 3-chloroperbenzoic acid. Useful reaction temperatures typically range from −78 to 90° C. Particular procedures useful for oxidizing sulfides to sulfoxides and sulfones are described by Brand et al., J. Agric. Food Chem. 1984, 32, 221-226 and references cited therein.

As shown in Scheme 2, compounds of Formula 1 in which X is NH and R^(1a) is H can be prepared by the reaction of 1H-pyrazole compounds of Formula 2 with various alkylating agents (e.g., Formula 3), such as iodoalkanes, alkylsulfonates (e.g., mesylate (OMs) or tosylate (OTs)) or trialkyl phosphates, preferably in the presence of an organic or inorganic base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium carbonate or potassium hydroxide, and in a solvent such as N,N-dimethylformamide, tetrahydrofuran, toluene or water.

Compounds of Formula 1 wherein CHR¹R^(1a) forms an optionally substituted cyclopropyl ring can likewise be prepared by reaction of a pyrazole of Formula 2 with an organometallic reagent, such as tricyclopropylbismuth, in the presence of a catalyst, such as copper acetate, under conditions known in the art. See, for example, J. Am. Chem. Soc. 2007, 129(1), 44-45. Of note as starting materials in the method of Scheme 2 are compounds of Formula 2 specifically disclosed in Tables 588 through 671 below.

As is shown in Scheme 3, compounds of Formula 1 can be prepared by the reaction of compounds of Formula 4 (i.e. 5-aminopyrazoles for X being NR⁴, 5-hydroxypyrazoles (5-pyrazolones) for X being O, or 5-mercaptopyrazoles for X being S) with aromatic compounds of Formula 5 containing a leaving group G (i.e. halogen or (halo)alkylsulfonate), optionally in the presence of a metal catalyst, and generally in the presence of a base and a polar aprotic solvent such as N,N-dimethylformamide or dimethyl sulfoxide. For example, compounds of Formula 5 in which Q² is an electron-deficient heteroaromatic ring, or a benzene ring with electron-withdrawing substituents, react by direct displacement of the leaving group G from the ring to provide compounds of Formula 1. For compounds of Formula 5 wherein Q² is attached through a sp³-hybridized carbon atom, G is typically Cl, Br, I or a sulfonate (e.g., OS(O)₂CH₃). Compounds of Formula 5 are commercially available or their preparation is known in the art. Of note are embodiments of the method of Scheme 3 wherein a compound of Formula 4 is used to prepare a corresponding compound of Formula 1 specifically disclosed in Tables 85 through 252 below.

For reactions according to the method of Scheme 3 of a compound of Formula 4 wherein X is O or NR⁴ with a compound of Formula 5 (Q²-G) wherein Q is an aromatic or heteroaromatic ring Q lacking sufficiently electron-withdrawing substituents, or to improve reaction rate, yield or product purity, the use of a metal catalyst (e.g., metal or metal salt) in amounts ranging from catalytic up to superstoichiometric can facilitate the desired reaction. Typically for these conditions, G is Br or I or a sulfonate such as OS(O)₂CF₃ or OS(O)₂(CF₂)₃CF₃. For example, copper salt complexes (e.g., CuI with N,N′-dimethyl-ethylenediamine, proline or bipyridyl), palladium complexes (e.g., tris(dibenzylidene-acetone)dipalladium(0)) or palladium salts (e.g., palladium acetate) with ligands such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (i.e. “Xantphos”), 2-dicyclohexyl-phosphino-2′,4′,6′-triisopropylbiphenyl (i.e. “Xphos”) or 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (i.e. “BINAP”), in the presence of a base such as potassium carbonate, cesium carbonate, sodium phenoxide or sodium tert-butoxide, in a solvent such as N,N-dimethylformamide, 1,2-dimethoxyethane, dimethyl sulfoxide, 1,4-dioxane or toluene, optionally mixed with alcohols such as ethanol, can be used. Alternatively as illustrated in Scheme 4, compounds of Formula 1c (i.e. Formula 1 in which X is NR⁴ and R⁴ is H) can be prepared by reaction of compounds of Formula 6 (i.e. 5-bromopyrazoles or other pyrazoles substituted at the 5-position with a leaving group) with compounds of Formula 7 under metal-catalyzed conditions similar to those described above for Scheme 3. Compounds of Formula 7 are commercially available or their preparation is known in the art.

As shown in Scheme 5, compounds of Formula 6 wherein G is Br or I can be prepared by reaction of 5-aminopyrazoles of Formula 4a (i.e. Formula 4 wherein X is NH) under diazotization conditions either in the presence of, or followed by combination with, copper salts containing bromide or iodide. For example, addition of tert-butyl nitrite to a solution of a 5-aminopyrazole of Formula 4a in the presence of CuBr₂ in a solvent such as acetonitrile provides the corresponding 5-bromopyrazole of Formula 6. Likewise, a 5-aminopyrazole of Formula 4a can be converted to a diazonium salt and then to a corresponding 5-halopyrazole of Formula 6 by treatment with sodium nitrite in solvents such as water, acetic acid or trifluoroacetic acid, in the presence of a mineral acid typically containing the same halide atom (such as aqueous HI solution for G being I), followed by treatment with the corresponding copper(I) or copper(II) salt according to general procedures well known to those skilled in the art.

As shown in Scheme 6, 5-bromopyrazoles of Formula 6a (i.e. Formula 6 wherein G is Br) can be prepared by reacting 5-hydroxypyrazoles of Formula 4b (i.e. Formula 4 wherein X is O) with phosphorus tribromide as described in Tetrahedron Lett. 2000, 41(24), 4713.

As shown in Scheme 7, 5-hydroxypyrazoles of Formula 4b can also be used to prepare 5-fluoroalkylsulfonyl (e.g, 5-trifluoromethanesulfonyl, 5-nonafluorobutylsulfonyl) pyrazoles of Formula 6b (i.e. Formula 6 wherein G is fluoroalkylsulfonyl) as described in Synlett 2004, 5, 795.

-   -   wherein Rf is fluoroalkyl such as CF₃ or (CF₂)₂CF₃

As shown in Scheme 8, compounds of Formula 1 can be prepared by reaction of 4-bromo or iodo pyrazoles of Formula 10 wherein X is O, NR⁴, C(═O) or S(O)_(m) in which m is 2 with organometallic compounds of formula Q¹-M (Formula 11) under transition-metal-catalyzed cross-coupling reaction conditions. Reaction of a 4-bromo or iodo pyrazole of Formula 10 with a boronic acid, trialkyltin, zinc or organomagnesium reagent of Formula 11 in the presence of a palladium or nickel catalyst having appropriate ligands (e.g., triphenylphosphine (PPh₃), dibenzylideneacetone (dba), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (SPhos)) and a base, if needed, affords the corresponding compound of Formula 1. For example, a substituted aryl boronic acid or derivative (e.g., Formula 11 wherein Q¹ is optionally substituted phenyl or heterocyclyl and M is B(OH)₂, B(OC(CH₃)₂C(CH₃)₂O)) or B(O-i-Pr)₃/Li— reacts with a 4-bromo- or 4-iodopyrazole of Formula 10 in the presence of dichlorobis(triphenylphosphine) palladium(II) and aqueous base such as sodium carbonate or potassium hydroxide, in solvents such as 1,4-dioxane, 1,2-dimethoxyethane, toluene or ethyl alcohol, or under anhydrous conditions with a ligand such as phosphine oxide or phosphite ligand (e.g., diphenylphosphine oxide) and potassium fluoride in a solvent such as 1,4-dioxane (see Angewandte Chemie, International Edition 2008, 47(25), 4695-4698) to provide the corresponding compound of Formula 1.

As illustrated in Scheme 9, compounds of Formula 4a (i.e. Formula 4 wherein X is NH) can be prepared by reacting compounds of Formula 12 with compounds of Formula 11 (such as Q¹-B(OH)₂ (Formula 11a)) using transition-metal-catalyzed cross-coupling reaction conditions as described for the method of Scheme 8.

As illustrated in Scheme 10, pyrazoles of Formula 10 wherein X is O, S(O)₂, NR⁴ or C(═O) and G is Br or I are readily prepared by the reaction of pyrazoles unsubstituted at the 4-position (Formula 13) with halogenating reagents such as bromine, sodium bromite, N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS), in solvents such as acetic acid, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide or 1,4-dioxane, or a mixture of water with the aforementioned solvents, at temperatures ranging from ambient to the boiling point of the solvent.

Furthermore, using reaction conditions similar to those for the method of Scheme 10, compounds of Formula 13 wherein A is H or a protecting group can be converted into intermediates corresponding to Formula 10 wherein Q² is replaced by A or a protecting group, respectively, which are useful for preparing compounds of Formula 1. Compounds of Formula 13 wherein A is H can be prepared by methods known in the art; see, for example, Synlett 2004, 5, 795-798, U.S. Pat. No. 4,256,902 and references cited therein. Furthermore, some compounds of Formula 13 wherein A is H, particularly those in which R² is methyl, ethyl or halogen, are commercially available.

As shown in Scheme 11, compounds of Formula 13 wherein X is O, S(O)_(m) or NR⁴, m is 0, and A is Q² can be prepared from corresponding compounds of Formula 13a (i.e. Formula 13 wherein A is H) by procedures analogous those used for the method of Scheme 3. Compounds of Formula 13 wherein X is S (i.e. S(O)_(m) wherein m is 0) can then be oxidized using procedures such as those used for the method of Scheme 1 to provide corresponding compounds of Formula 13 wherein X is S(O)₂ for use in the method of Scheme 10. Compounds of Formula 13a are commercially available or can be prepared by methods known in the art.

As shown in Scheme 12, compounds of Formula 1a (i.e. Formula 1 wherein X is S(O)_(m) and m is 0), Formula 1d (i.e. Formula 1 wherein X is CR¹⁵R¹⁶, R¹⁵ is H, R¹⁶ is OR¹⁸ and R¹⁸ is H) and Formula 1e (i.e. Formula 1 wherein X is C(═O)) can be prepared by treatment of compounds of Formula 6 with an organometallic reagent (i.e. Formula 26) such as an alkyllithium, preferably n-butyllithium, or an alkylmagnesium reagent, preferably isopropylmagnesium chloride (optionally complexed with lithium chloride), followed by the addition of a sulfur electrophile (i.e. Formula 27) or carbonyl electrophile (i.e. Formula 28, 29 or 30). Reaction temperatures can range from −90° C. to the boiling point of the reaction solvent; temperatures of −78° C. to ambient temperature are generally preferred, with temperatures of −78 to −10° C. preferred when an alkyllithium reagent is used, and −20° C. to ambient temperature preferred with use of alkylmagnesium reagents. A variety of solvents are useful, such as toluene, ethyl ether, tetrahydrofuran or dimethoxymethane; anhydrous tetrahydrofuran is preferred. A second metallic component, such as zinc chloride, zinc bromide or a monovalent copper salt, such as copper(I) iodide or copper(I) cyanide, can advantageously be added before the electrophile in cases in which the electrophile is Q²C(O)Cl (i.e. Formula 30). The Q²-containing sulfur and carbonyl intermediates of Formulae 27, 28, 29 and 30 are commercially available or can be prepared by methods known in the art.

It will be recognized by one skilled in the art that reactions analogous to those shown in Scheme 12 can also be utilized with pyrazoles lacking a Q¹ substituent, thus affording certain compounds of Formula 13 that are useful in the method outlined in Scheme 10.

General methods useful for preparing 5-aminopyrazoles of Formula 4a are well known in the art; see, for example, Journal fir Praktische Chemie (Leipzig) 1911, 83, 171 and J. Am. Chem. Soc. 1954, 76, 501. Such a method is illustrated in Scheme 13 in which R² is alkyl or cycloalkyl.

Similarly, general methods useful for preparing 5-hydroxypyrazoles of Formula 4b are well known in the art; see, for example, Annalen der Chemie 1924, 436, 88. Such a method is illustrated in Scheme 14 in which R² is alkyl or cycloalkyl.

As shown in Scheme 15, 5-thiopyrazole compounds of Formula 4c (i.e. Formula 4 wherein X is S) can be prepared by reaction of corresponding 5-hydroxypyrazole compounds of Formula 4b with P₂S₅ (see, for example, Justus Liebigs Annalen der Chemie 1908, 361, 251) or with Lawesson's Reagent (2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide; see, for example, International Patent Publication WO 2005/118575) in solvents such as toluene, xylene or tetrahydrofuran.

As shown in Scheme 16, compounds of Formula 1c (i.e. Formula 1 wherein X is NR⁴ and R⁴ is H) can be prepared by condensing compounds of Formula 17 with alkylhydrazines of Formula 15 in a solvent such as ethanol or methanol and optionally in the presence of an acid or base catalyst such as acetic acid, piperidine or sodium methoxide, according to general procedures known in the art.

-   -   wherein R³² is H or lower alkyl (e.g., CH₃, CH₂CH₃ or (CH₂)₂CH₃)

In a manner analogous to the method of Scheme 16, compounds of Formula 2 wherein X is NH can be similarly prepared by condensing compounds of Formula 17 with hydrazine. This method is described in Chemistry of Heterocyclic Compounds 2005, 41(1), 105-110.

As shown in Scheme 17, compounds of Formula 17 (wherein, e.g., R² is methyl, ethyl or optionally substituted cyclopropyl and R³³ is H or lower alkyl such as CH₃, CH₂CH₃ or (CH₂)₂CH₃) can be prepared by reaction of corresponding ketene dithioacetal compounds of Formula 18 with compounds of formula Q²-NH₂ (i.e. Formula 7) optionally in the presence of a base, such as sodium hydride or ethylmagnesium chloride, in solvents such as toluene, tetrahydrofuran or dimethoxymethane, at temperatures ranging from −10° C. to the boiling point of the solvent. See, for example, J. Heterocycl. Chem. 1975, 12(1), 139. Methods useful for preparing compounds of Formula 18 are known in the art.

-   -   wherein R³³ is H or lower alkyl (e.g., CH₃, CH₂CH₃ or (CH₂)₂CH₃)

It is also known in the art (see, for example, Synthesis 1989, 398) that compounds of Formula 18 in which the two R³³ groups are taken together as a single CH₂ group (thus forming a dithietane ring) react with an stoichiometric excess amount of hydrazines of Formula 15 to afford compounds of Formula 4c, which are useful for preparation of compounds of Formula 1 in which X is S according to the method of Scheme 3.

As shown in Scheme 18, compounds of Formula 17a (i.e. tautomer of Formula 17 wherein R³³ is H) can be prepared by reaction of corresponding isothiocyanate compounds of Formula 19 with arylacetone compounds of Formula 20 wherein R² is methyl, ethyl or optionally substituted cyclopropyl; see, for example, Zhurnal Organicheskoi Khimii 1982, 18(12), 2501. Bases useful for this reaction include sodium hydride, alkoxide bases (e.g., potassium tert-butoxide or sodium ethoxide), potassium hydroxide, sodium hydroxide, potassium carbonate, or amine bases (e.g., triethylamine or N,N-diisopropylethylamine). A variety of solvents are useful, such as tetrahydrofuran, ether, toluene, N,N-dimethylformamide, alcohols (e.g., ethanol), esters (e.g., ethyl acetate or isopropyl acetate), or mixtures thereof. Solvents are chosen for compatibility with the base selected, as is well-known in the art. Reaction temperatures can range from −78° C. to the boiling point of the solvent. One useful mixture of base and solvent is potassium tert-butoxide in tetrahydrofuran, to which at −70 to 0° C. is added a combined solution of an isothiocyanate of Formula 19 and a carbonyl compound of Formula 20.

Ketothioamides of Formula 17 can be also be prepared by allowing the corresponding ketoamides to react with sulfurizing agents such as Lawesson's reagent or P₂S₅; see, for example, Helv. Chim. Act. 1998, 81(7), 1207.

Compounds of Formula 2 wherein X is NH and R² is Cl or Br, which are useful for preparing compounds of Formula 1 according to the method of Scheme 2, can be prepared by reaction of corresponding compounds of Formula 31 with POCl₃ or POBr₃ using general procedures known in the art, as shown in Scheme 19.

As shown in Scheme 20, compounds of Formula 1f (i.e. Formula 1 wherein R¹ and R^(1a) are H and R² is OCH₃) can be prepared by reacting corresponding compounds of Formula 31 with diazomethane or iodomethane in the presence of base using general procedures known in the art, such as those described in J. Heterocyclic Chem. 1988, 1307-1310.

Compounds of Formula 1g (i.e. Formula 1 wherein R¹ and R^(1a) are H and R² is SCH₃) can be prepared by treating corresponding compounds of Formula 31 with P₂S₅ or Lawesson's Reagent to prepare compounds of Formula 32, which are then reacted with diazomethane or iodomethane in the presence of base using general procedures known in the art, as shown in Scheme 21.

As shown in Scheme 22, compounds of Formula 31 wherein X is NH can be prepared by condensation of corresponding isothiocyanates of Formula 19 with esters of Formula 33 wherein R³³ is lower alkyl (e.g., methyl, ethyl, propyl) in the presence of a strong, non-nucleophilic base such as sodium hydride or lithium hexamethyldisilazide, in an inert solvent such as tetrahydrofuran (analogous to the method of Scheme 18), followed by reaction of the intermediate with hydrazine or an acid salt of hydrazine, such as, for example, an acetate or hydrochloride salt (analogous to the method of Scheme 16).

One skilled in the art will recognize that use of a substituted hydrazine of formula H₂NNHCHR¹R^(1a) instead of unsubstituted hydrazine in the method of Scheme 22, followed by the further manipulations described for Schemes 19, 20 and 21 will also afford compounds of Formula 1.

Compounds of Formula 1c (i.e. Formula 1 wherein X is NR⁴ and R⁴ is H) in which R² is halogen can also be prepared as shown in Scheme 23. In this method an acetonitrile compound of Formula 21 is condensed with an isothiocyanate compound of Formula 22 in the presence of a base such as sodium hydride or potassium tert-butoxide, in a solvent such as N,N-dimethylformamide or tetrahydrofuran, to afford a cyano ketoamide intermediate compound, which is then reacted with a methylating agent such as iodomethane or dimethyl sulfate, in the presence of a base to provide the corresponding compound of Formula 23. Alternatively, the methylating agent can be included in the reaction mixture with the compounds of Formulae 21 and 22 without isolation of the cyano ketoamide intermediate. One skilled in the art will recognize that compounds of Formula 23 can also be prepared by a method analogous to Scheme 17 wherein the C(O)R² of the compound of Formula 18 is replaced by cyano. According to the method of Scheme 23, the resultant compound of Formula 23 is then reacted with an alkylhydrazine of Formula 15 to form the corresponding 3-aminopyrazole compound of Formula 24 using general procedures known in the art; see, for example, J. Chem. Soc. Perkin 1 1988, 2, 169-173 and J. Med. Chem. 2003, 46(7), 1229-1241. The amino group of the compound of Formula 24 can then be converted to R² being halogen in Formula 1c by a diazotization reaction using conditions known in the art, such as those previously described for Scheme 5.

Analogous to the method of Scheme 23, compounds of Formula 2 wherein X is NH and R² is halogen can be similarly prepared by condensing compounds of Formula 23 with hydrazine instead of an alkylhydrazine of Formula 15.

As shown in Scheme 24, compounds of Formula 1h (i.e. Formula 1 wherein X in NR⁴) can be prepared by reacting corresponding compounds of Formula 1c (i.e. Formula 1 wherein X is NH) with an electrophile comprising R⁴ (i.e. Formula 25) typically in the presence of a base such as NaH and a polar solvent such as N,N-dimethylformamide. In this context the expression “electrophile comprising R⁴” means a chemical compound capable of transferring an R⁴ moiety to a nucleophile (such as the nitrogen atom attached to Q² in Formula 1c). Often electrophiles comprising R⁴ have the formula R⁴Lg wherein Lg is a nucleofuge (i.e. leaving group in nucleophilic reactions). Typical nucleofuges include halogens (e.g., Cl, Br, I) and sulfonates (e.g., OS(O)₂CH₃, OS(O)₂CF₃, OS(O)₂-(4-CH₃-Ph)). However, some electrophiles comprising R⁴ do not comprise a nucleofuge; an example is sulfur trioxide (SO₃), which after deprotonation (such as by a base of the formulae M⁺H⁻ wherein M⁺ is a cation) of the nitrogen atom attached to Q² in Formula 1c, can bond to the nitrogen atom as a —SO₃ ⁻M⁺ substituent.

It is recognized by one skilled in the art that various functional groups can be converted into others to provide different compounds of Formula 1. For example, compounds of Formula 1 in which R² is methyl, ethyl or cyclopropyl can be modified by free-radical halogenation to form compounds of Formula 1 wherein R² is halomethyl, haloethyl or halocyclopropyl. The halomethyl compounds can be used as intermediates to prepare compounds of Formula 1 wherein R² is hydroxymethyl or cyanomethyl. Compounds of Formula 1 or intermediates for their preparation may contain aromatic nitro groups, which can be reduced to amino groups, and then be converted via reactions well known in the art such as the Sandmeyer reaction, to various halides, providing other compounds of Formula 1. By similar known reactions, aromatic amines (anilines) can be converted via diazonium salts to phenols, which can then be alkylated to prepare compounds of Formula 1 with alkoxy substituents. Likewise, aromatic halides such as bromides or iodides prepared via the Sandmeyer reaction can react with alcohols under copper-catalyzed conditions, such as the Ullmann reaction or known modifications thereof, to provide compounds of Formula 1 that contain alkoxy substituents. Additionally, some halogen groups, such as fluorine or chlorine, can be displaced with alcohols under basic conditions to provide compounds of Formula 1 containing the corresponding alkoxy substituents. The resultant alkoxy compounds can themselves be used in further reactions to prepare compounds of Formula 1 wherein R³ is —U—V-T (see, for example, PCT Publication WO 2007/149448 A2). Compounds of Formula 1 or precursors thereof in which R² or R³ is halide, preferably bromide or iodide, are particularly useful intermediates for transition metal-catalyzed cross-coupling reactions to prepare compounds of Formula 1. These types of reactions are well documented in the literature; see, for example, Tsuji in Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis, John Wiley and Sons, Chichester, 2002; Tsuji in Palladium in Organic Synthesis, Springer, 2005; and Miyaura and Buchwald in Cross Coupling Reactions: A Practical Guide, 2002; and references cited therein.

One skilled in the art will recognize that sulfide groups can be oxidized to the corresponding sulfoxides or sulfones by conditions well-known in the art. Likewise, compounds of Formula 1 wherein X is CR¹⁵R¹⁶, R¹⁵ is H, R¹⁶ is OR¹⁸ and R¹⁸ is H can be readily interconverted with corresponding compounds of Formula 1 wherein X is C(═O) by alcohol oxidation and ketone reduction reactions well known in the art. Compounds of Formula 1 wherein X is C(═O) (i.e. ketones) can be readily converted to ketals using general methods known in the art, thus providing compounds of Formula 1 wherein X is CR¹⁵R¹⁶ and R¹⁵ and R¹⁶ are taken together as —OCH₂CH₂O—. Compounds of Formula 1 wherein X is C(═O) can also be converted by the use of Lawesson's Reagent to prepare corresponding compounds of Formula 1 wherein X is C(═S). Furthermore, compounds of Formula 1 wherein X is CR¹⁵R¹⁶, R¹⁵ is C₁-C₄ alkyl, R¹⁶ is OR¹⁸, and R¹⁸ is H can be prepared by adding an alkyl Grignard reagent to the corresponding compounds of Formula 1 wherein X is C(═O).

The above reactions can also in many cases be performed in alternate sequence, such as the preparation of 1H pyrazoles for use in the reaction in Scheme 2 by reactions illustrated later for the general preparation of substituted pyrazoles. The presence of certain functional groups may not be compatible with all of these reaction conditions, and the use of protecting groups may be desirable for obtaining the desired products with improved yields and or purity.

It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula 1. One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Synthesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Synthesis Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. ¹H NMR spectra are reported in ppm downfield from tetramethylsilane in CDCl₃ unless otherwise noted; “s” means singlet, “m” means multiplet, “br s” means broad singlet. Mass spectra are reported as the molecular weight of the highest isotopic abundance parent ion (M+1) formed by addition of H⁺ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP⁺) where “amu” stands for atomic mass units.

Synthesis Example 1 Preparation of N-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 1) Step A: Preparation of α-Acetyl-2,4-difluorobenzeneacetonitrile (Alternatively Named methyl α-cyano-2,4-difluorobenzeneacetate)

Sodium hydride (60% in mineral oil) (1.5 g, 38 mmol) was stirred in xylenes (7 mL) under a nitrogen atmosphere at ambient temperature. A solution of anhydrous ethanol (6.3 mL, 64 mmol) in xylenes (2 mL) was added dropwise over about 20 minutes at a temperature of about 40° C. The reaction mixture was heated to 70° C., and a solution of 2,4-difluorophenylacetonitrile (3.9 g, 25 mmol), ethyl acetate (3.8 mL, 38 mmol) and xylenes (1 mL) was added dropwise over 15 min. Additional xylenes (5 mL) was added to aid stirring. The reaction mixture was heated for 2 h, then allowed to cool. Water (50 mL) was added, and the mixture was extracted with hexanes (50 mL). The aqueous phase was then acidified to pH 3-4 with 1 N aqueous HCl solution. The aqueous phase was extracted with ether (50 mL), and the ethereal extract was washed with water (25 mL) and brine, then dried over MgSO₄, and concentrated to give the title compound as a viscous residue (3.3 g). ¹H NMR δ 7.42 (m, 1H), 6.8-7.0 (m, 2H), 4.95 (s, 1H), 2.36 (s, 3H).

Step B: Preparation of 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine

Acetic acid (0.5 mL, 8.3 mmol) and methylhydrazine (534 μL, 10.0 mmol) were added to a solution of the residue obtained in Step A (1.6 g, 8.5 mmol) in ethyl alcohol (8 mL). The reaction mixture was then heated at reflux for 16 h under a nitrogen atmosphere. While the reaction mixture was still warm, water was added in small portions (1 mL at a time) until a precipitate formed (about 12 mL of water total). The mixture was reheated to dissolve the solids and then allowed cooled to room temperature. The resulting precipitate was collected on a glass frit, washed with 2 to 3 mL of 50% aqueous ethyl alcohol, and dried under vacuum to obtain the compound as a white solid (0.99 g).

¹H NMR δ 7.20 (m, 1H), 6.92 (m, 2H), 3.68 (s, 3H), 3.47 (br s, 2H), 2.14 (s, 3H).

Step C: Preparation of N-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine

Palladium(II) acetate (90 mg, 0.40 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (460 mg, 0.80 mmol) and powdered potassium carbonate (5.5 g, 40 mmol) were combined in anhydrous 1,4-dioxane (20 mL), and the mixture was sparged with a subsurface stream of N₂ gas for 10 min. 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (i.e. the product of Step B) (0.89 g, 4.0 mmol) was added in one portion, and 1-bromo-3-chlorobenzene (0.47 mL, 4.0 mmol) was added via a syringe. The reaction mixture was heated at reflux under a nitrogen atmosphere for 3 h. Additional 1-bromo-3-chlorobenzene (0.09 mL, 0.8 mmol) was added, and heating was continued for 1 h. The reaction mixture was allowed to cool to room temperature, and then partitioned between water (40 mL) and ethyl acetate (40 mL). The organic phase was washed with additional water (40 mL), brine (40 mL), dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by column chromatography through 10 g of silica gel eluted with hexanes/ethyl acetate (1:1) to give the title compound, a compound of the present invention, as a solid (0.41 g).

¹H NMR δ 7.2-7.3 (m, 2H), 7.10 (m, 1H), 6.9-7.0 (m, 2H), 6.70 (m, 1H), 6.58 (m, 1H), 6.52 (m, 1H), 3.64 (s, 3H), 2.14 (s, 3H). MS: 334 amu.

Synthesis Example 2 Preparation of 4-(2-Chloro-4-fluorophenyl)-N-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 17) Step A: Preparation of 5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole

Copper(II) bromide (3.94 g, 17.7 mmol) was added to a solution of 4-[2-chloro-4-fluorophenyl]-1,3-dimethyl-1H-pyrazol-5-amine (prepared similarly to the preparation of 4-(2,4-Difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine in Steps A and B of Synthesis Example 1) (2.4 g, 10 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyl nitrite (90% technical grade, 2.33 mL, 17.7 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous HCl solution (20 mL) was added, and then ethyl acetate was added (20 mL). This mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (20 mL), and the phases were separated. The organic phase was washed with 1.0 N aqueous hydrochloric acid solution and brine, dried over MgSO₄, and concentrated to leave the title compound as an orange-brown semisolid (2.8 g).

¹H NMR δ 7.18-7.25 (m, 2H), 7.04 (m, 1H), 3.89 (s, 3H), 2.14 (s, 3H).

Step B: Preparation of 4-(2-Chloro-4-fluorophenyl)-N-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-amine

5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step A) (0.20 g, 0.66 mmol), palladium(II) acetate (15 mg, 0.066 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (76 mg, 0.13 mmol) and powdered potassium carbonate (1.8 g, 13 mmol) were combined in anhydrous 1,4-dioxane (3 mL), and the mixture was sparged with a subsurface stream of N₂ gas for 10 min. 2,6-Difluoro-4-methoxyaniline (0.22 g, 1.3 mmol) was added in one portion, and the reaction mixture was heated at reflux for 22 h. The reaction mixture was filtered through Celite® diatomaceous filter aid, and the filter pad was washed with ethyl acetate (20 mL). The filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO₄, and concentrated to leave a semisolid residue. This residue was purified by column chromatography through 5 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3) to give the title compound, a compound of the present invention, as a light-brown solid (48 mg).

¹H NMR δ 7.0-7.1 (m, 2H), 6.85 (m, 1H), 6.26 (m, 2H), 4.84 (br s, 1H), 3.78 (s, 3H), 3.66 (s, 3H), 2.08 (s 3H). MS: 382 amu.

Synthesis Example 3 Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine (Compound 24) Step A: Preparation of 2,6-Difluoro-4-methoxybenzeneacetonitrile

A solution of KCN (0.88 g, 13 mmol) dissolved in water (2 mL) was added dropwise to a water-bath-cooled solution of 2,6-difluoro-4-methoxybenzyl bromide (2.50 g, 10.5 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was stirred for 20 min. Water was added (20 mL) and then the reaction mixture was poured into saturated aqueous NaHCO₃ solution (20 mL) and extracted with ether (50 mL). The organic phase was washed with water (5×25 mL), dried over MgSO₄, and concentrated to give an oil, which crystallized on standing to provide the title compound as a white solid (1.9 g).

¹H NMR δ 6.50 (m, 2H), 3.80 (s, 3H), 3.65 (s, 2H).

Step B: Preparation of ca-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile

Solid sodium ethoxide (4.7 g, 66 mmol) was stirred in a mixture of xylene (20 mL) and ethanol (10 mL) and heated to 50° C. A solution of 2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step A) (8.0 g, 44 mmol) in ethyl acetate (10.4 mL) was added dropwise. The reaction mixture was heated at 50° C. for 4 h and then allowed to cool to ambient temperature. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (25 mL). The aqueous phase was acidified with 3 N aqueous HCl to pH 4 and extracted with ethyl acetate (100 mL). This organic phase was washed with water (50 mL), brine (50 mL), then dried over MgSO₄, and concentrated to leave the title compound as a tan semisolid (8.0 g).

¹H NMR δ 6.56 (m, 2H), 4.86 (s, 1H), 3.83 (s, 3H), 2.40 (s, 3H).

Step C: Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole-5-amine

α-Acetyl-2,6-difluoro-4-methoxybenzeneacetonitrile (i.e. the product of Step B) (8.03 g, 35.7 mmol) and acetic acid (5 mL) were stirred in ethanol (35 mL), and methylhydrazine (1.91 mL, 35.7 mmol) was added. The reaction mixture was heated at reflux for 16 h, cooled, and then poured into water (100 mL). The resulting mixture was extracted with ethyl acetate (100 mL). The organic phase was washed with 1 N aqueous NaOH (50 mL) and then brine (50 mL), dried over MgSO₄, and concentrated to leave a solid. The solid was dissolved in methanol, and the resulting solution was warmed to 45° C.

Water (25 mL) was added dropwise, and the mixture was allowed to cool. The precipitate was collected on a glass frit to give the title compound as a white solid (3.88 g).

¹H NMR δ 6.55 (m, 2H), 3.81 (s, 3H), 3.67 (s, 3H), 3.43 (br s, 2H), 2.09 (s, 3H).

Step D: Preparation of 5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole

Copper(II) bromide (3.81 g, 16.9 mmol) was added to a solution of 4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step C) (3.88 g, 15.4 mmol) in acetonitrile (50 mL), and the mixture was stirred and cooled in an ice-water bath while tert-butyl nitrite (90% technical grade, 3.54 mL, 26.9 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm slowly to ambient temperature. Aqueous hydrochloric acid solution (25 mL) was added, then ethyl acetate (25 mL) was added, and the resulting mixture was filtered through a 2-cm pad of Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (50 mL), and the phases were separated. The organic phase was washed with 1 N aqueous HCl solution (25 mL) and brine (25 mL), dried over MgSO₄, and concentrated. The residue was purified by column chromatography through 24 g of silica gel eluted with a gradient of hexanes/ethyl acetate (9:1 to 1:1) to give the title compound as a white solid (3.25 g).

¹H NMR δ 6.54 (m, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 2.16 (s, 3H).

Step E: Preparation of 4-(2,6-Difluoro-4-methoxyphenyl)-1,3-dimethyl-N-(2,4,6-trifluorophenyl)-1H-pyrazol-5-amine

5-Bromo-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step D) (0.30 g, 0.94 mmol), palladium(II) acetate (20 mg, 0.090 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.11 g, 0.19 mmol) and powdered potassium carbonate (2.6 g, 19 mmol) were combined in anhydrous 1,4-dioxane (4 mL), and the resulting mixture was sparged with a subsurface stream of N₂ gas for 10 min. 2,4,6-Trifluoroaniline (0.28 g, 1.9 mmol) was added in one portion, and the reaction mixture was heated at reflux under nitrogen for 22 h. The reaction mixture was cooled, then filtered through Celite® diatomaceous filter aid. The filter pad was washed with ethyl acetate (20 mL), and the filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO₄, and concentrated to leave a semisolid residue. The residue was purified by column chromatography through 12 g of silica gel eluted with a gradient of hexanes/ethyl acetate (20:1 to 1:3) to give the title compound, a compound of the present invention, as a semisolid (73 mg).

¹H NMR (acetone-d₆) δ 6.84 (br s, 1H), 6.68 (m, 2H), 6.43 (m, 2H), 3.77 (s, 3H), 3.75 (s, 3H), 1.99 (s, 3H). MS: 384 amu (AP⁺).

Synthesis Example 4 Preparation of 4-[[4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile (Compound 45) Step A: Preparation of 4-[(1,3-Dimethyl-1H-pyrazol-5-yl)oxy]-3,5-difluorobenzonitrile

Potassium carbonate (1.38 g, 10 mmol) was added to a solution of 2,4-dihydro-2,5-dimethyl-3H-pyrazol-3-one (0.70 g, 6.3 mmol) in N,N-dimethylformamide (15 mL). 3,4,5-Trifluorobenzonitrile (0.94 g, 6.0 mmol) was added, and the reaction mixture was heated at 75° C. under a nitrogen atmosphere for 16 h, then allowed to cool. The reaction mixture was partitioned between water (60 mL) and ethyl acetate (30 mL). The organic phase was washed with water (2×30 mL) and brine (30 mL), dried over MgSO₄, and concentrated to give the title compound as a yellow oil (1.38 g).

¹H NMR δ 7.36 (m, 2H), 5.24 (s, 1H), 3.78 (s, 3H), 2.16 (s, 3H).

Step B: Preparation of 3,5-Difluoro-4-[(4-iodo-1,3-dimethyl-1H-pyrazol-5-yl)oxy]benzonitrile

A solution of 4-[(1,3-dimethyl-1H-pyrazol-5-yl)oxy]-3,5-difluorobenzonitrile (i.e. the product of Step A) (1.38 g, 5.5 mmol) in acetonitrile (20 mL) was stirred at ambient temperature, and N-iodosuccinimide (1.35 g, 6.0 mmol) was added in one portion. The reaction mixture was heated at reflux for 2 h, cooled, and then poured into water (40 mL). The resulting mixture was extracted with ethyl acetate (40 mL). The organic phase was washed with water (20 mL) and saturated aqueous NaHCO₃ solution (20 mL), dried over MgSO₄, and concentrated under reduced pressure to give the title compound as a tan solid (2.1 g).

¹H NMR (acetone-d₆) δ 7.80 (m, 2H), 3.82 (s, 3H), 2.09 (s, 3H). MS: 376 amu (AP⁺).

Step C: Preparation of 4-[[4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile

To a solution of 3,5-difluoro-4-[(4-iodo-1,3-dimethyl-1H-pyrazol-5-yl)oxy]-benzonitrile (i.e. the product of Step B) (1.0 g, 2.67 mmol) in 1,4-dioxane (6 mL) was added 2-chloro-4-fluorobenzeneboronic acid (alternatively named B-(2-chloro-4-fluorophenyl)-boronic acid) (0.93 g, 5.33 mmol), dichloro (bis)triphenylphosphine palladium(II) (alternatively named bis(triphenylphosphine)palladium(II) dichloride) (93 mg, 0.13 mmol), potassium carbonate (0.74 g, 5.33 mmol), and water (4 mL). The resulting mixture was heated at reflux for 5 h, allowed to cool, and partitioned between water (20 mL) and ethyl acetate (20 mL). The organic layer was dried over MgSO₄ and concentrated. The residue was purified by chromatography on silica gel with a gradient of hexanes/ethyl acetate to obtain the title compound, a compound of the present invention, as an off-white solid (110 mg).

¹H NMR δ 7.00-7.09 (m, 3H), 6.97 (m, 1H), 6.86 (m, 1H), 3.85 (s, 3H), 2.02 (s, 3H).

Synthesis Example 5 Preparation of 4-(2,4-Dichlorophenyl)-N-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine (Compound 69) Step A: Preparation of α-Acetyl-2,4-dichloro-N-(2,4-difluorophenyl)benzeneethanethioamide

2,4-Difluorophenyl isothiocyanate (0.27 mL, 2.0 mmol) was added to a stirred suspension of sodium hydride (60% in mineral oil) (112 mg, 2.8 mmol) in anhydrous tetrahydrofuran (4 mL) cooled in an ice-water bath under a nitrogen atmosphere. A solution of (2,4-dichlorophenyl)-2-propanone (570 mg, 2.8 mmol) in tetrahydrofuran (4 mL) was added dropwise over 5 min. The resultant yellow solution was stirred at 5-10° C. for 1 h. Water (10 mL) was carefully added, and the reaction mixture was extracted with ethyl acetate (10 mL). The aqueous phase was acidified to pH 3 with 1 N aqueous HCl, then extracted with ethyl acetate (20 mL). The organic extract was washed with water (10 mL) and brine (10 mL), dried over MgSO₄, and concentrated to leave a solid. The solid was triturated with hexanes/ethyl acetate (2:1), collected on a glass frit, and air-dried to give the title compound as a white solid (240 mg). MS: 373 amu (AP⁺).

Step B: Preparation of 4-(2,4-Dichlorophenyl)-N-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine

Acetic acid (50 μL) and methylhydrazine (41 μL) were added to a stirred suspension of α-acetyl-2,4-dichloro-N-(2,4-difluorophenyl)benzeneethanethioamide (238 mg, 0.64 mmol) in ethanol (4 mL). The reaction mixture was heated at reflux for 2 h and allowed to cool. Then the reaction mixture was diluted with ethyl acetate (10 mL) and washed with 1 N aqueous NaOH (10 mL), water (10 mL) and brine (10 mL), dried over MgSO₄, and concentrated to leave a solid residue. The residue was purified by column chromatography on 5 g of silica gel with a gradient of hexanes/ethyl acetate (2:1 to 1:1) to give the title compound as a solid (170 mg).

¹H NMR δ 7.43 (s, 1H), 7.19 (m, 1H), 7.07 (m, 1H), 6.78 (m, 1H), 6.62 (m, 1H), 6.37 (m, 1H), 5.22 (br s, 1H), 3.70 (s, 3H), 2.18 (s, 3H). MS: 368 amu (AP⁺).

Synthesis Example 6 Preparation of 4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (Compound 351)

5-Bromo-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Synthesis Example 2, Step A) (0.25 g, 0.82 mmol) was dissolved in anhydrous tetrahydrofuran (12 mL), and the mixture was cooled in a dry ice/acetone bath under a nitrogen atmosphere. A cyclohexane solution of n-butyllithium (2.0 M, 0.49 mL, 0.98 mmol) was added dropwise over 5 minutes. After 15 minutes, a solution of 2,4-difluorobenzaldehyde (0.09 mL, 0.82 mmol) in anhydrous tetrahydrofuran (3 mL) was added slowly dropwise, causing the dark red-colored solution to lighten to a yellow color. After 45 minutes, the reaction mixture was quenched by the addition of saturated aqueous NH₄Cl solution (˜20 mL) and allowed to warm to ambient temperature. This mixture was extracted with ethyl acetate, and the organic phase was washed with saturated aqueous NH₄Cl solution (25 mL) and with brine, dried over Na₂SO₄, and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (7% to 10%) to give the title product, a compound of the present invention, as a white semi-solid (109 mg).

¹H NMR δ 7.5 (m, 1H), 7.1 (m, 2H), 7.0 (m, 1H), 6.85 (m, 2H), 6.0 (br s, 1H), 5.9 (s, 1H), 3.8 (s, 3H), 2.1 (s, 3H). MS: 367 amu (AP⁺).

Synthesis Example 7 Preparation of [4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl](2,4-difluorophenyl)methanone (Compound 370)

4-(2-Chloro-4-fluorophenyl)-α-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazole-5-methanol (i.e. the product of Synthesis Example 6) (90 mg, 0.25 mmol) was dissolved in dichloromethane (8 mL), and pyridinium dichromate (113 mg, 0.3 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 16 h, and then the reaction mixture was partitioned between water (5 mL) and dichloromethane (5 mL). The organic phase was washed with additional water (5 mL) and with brine (5 mL), dried over Na₂SO₄ and concentrated under reduced pressure to give a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate in hexane (25% to 30%) to give the title product, a compound of the present invention, as a pale yellow viscous oil (29 mg).

¹H NMR δ 7.94 (m, 1H), 7.32 (s, 1H), 7.27 (m, 1H), 7.03 (m, 1H), 6.95 (m, 1H), 6.78 (m, 1H), 3.82 (s, 3H), 2.13 (s, 3H). MS: 365 amu (AP⁺).

Synthesis Example 8 Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole (Compound 54) Step A: Preparation of Methyl 2,4,6-trifluorobenzeneacetate

A solution of 2,4,6-trifluorobenzeneacetic acid (5.00 g, 26.3 mmol) in methanol (25 mL) was stirred at ambient temperature, and thionyl chloride (6 mL, ˜3 eq.) was added dropwise, causing the temperature of the reaction mixture to reach 60° C. The reaction mixture was allowed to cool to ambient temperature and was stirred for 3 h. Water (25 mL) was added with ice cooling. The mixture was extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×), with saturated aqueous sodium bicarbonate solution and with brine, and dried over MgSO₄. Concentration provided the title product as a clear oil (5.38 g).

¹H NMR δ 6.68 (m, 2H), 3.72 (s, 3H), 3.66 (s, 2H).

Step B: Preparation of Methyl α-acetyl-2,4,6-trifluorobenzeneacetate

To a commercially obtained tetrahydrofuran solution of lithium bis(trimethyl-silyl)amide (1.0 M, 21.0 mL), stirred under a nitrogen atmosphere and cooled to an internal temperature of −65° C., was added dropwise over 30 minutes a solution of methyl 2,4,6-trifluorobenzeneacetate (i.e. the product of Step A) (2.04 g, 10.0 mmol) dissolved in dry tetrahydrofuran (10 mL). The reaction mixture was stirred for an additional 30 minutes, and then while maintaining the −65° C. temperature, a solution of freshly distilled acetyl chloride (0.80 mL, 11 mmol) in dry tetrahydrofuran (3 mL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature, and then water (30 mL) was added. The resultant mixture was extracted with ethyl acetate (60 mL). The aqueous phase was acidified with 1 N hydrochloric acid and extracted with ethyl acetate (60 mL). Only the first extract was retained, because thin layer chromatographic analysis showed the second extract to contain apparent polar impurities besides additional desired product. The initial organic phase was further washed with 1 N hydrochloric acid, water and brine, dried over MgSO₄, and concentrated to provide the title product as a clear oil (1.86 g).

¹H NMR δ 6.69 (m, 2H), 3.7 (m, 1H and s, 3H), 1.87 (s, 3H); minor resonances at 13.2 ppm and 4.9 ppm indicated presence of enolic tautomer.

Step C: Preparation of 1,3-Dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazol-5-ol

To a solution of methyl α-acetyl-2,4,6-trifluorobenzeneacetate (i.e. the product of Step B) (2.46 g, 10.0 mmol) in methanol (15 mL) was added methylhydrazine (0.665 mL, 12.5 mmol), and the mixture was stirred at ambient temperature over 3 days. Aqueous citric acid solution (1 M, 10 mL) was added, and then water (50 mL) was added. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with water and with brine, dried over MgSO₄, and concentrated to leave a yellow solid. This solid was suspended in a small volume of ethyl acetate (about 5 mL), an equal volume of hexanes was gradually added, and the suspension was stirred for 30 minutes. The solid component was collected on a glass frit, washed with small portions of ethyl acetate/hexanes (1:1 and 1:2 v:v), and allowed to dry in air to provide a white solid (1.02 g). Evaporation of the mother liquor and treatment of the resultant residue with small volumes of ethyl acetate and hexanes as already described provided an additional 0.13 g of solid containing the title product (1.15 g total). Analysis of the combined solids by LC/MS showed a primary component of mass 242 (AP+) and a minor component, eluting later by reverse-phase LC, also having a mass of 242 (AP+). The apparent ratio of components was 94:6.

¹H NMR (acetone-d₆) δ 6.95 (m, 2H), 3.52 (s, 3H), 1.98 (s, 3H); 5-hydroxy resonance was not observed in this solvent.

Step D: Preparation of 5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole

1,3-Dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazol-5-ol (i.e. the product of Step C) (0.310 g, 1.28 mmol), was combined with 3,4,5-trifluoronitrobenzene (157 μL, 1.35 mmol) and potassium carbonate powder (0.27 g, 2 mmol) in dry N,N-dimethylformamide (4 mL). This mixture was stirred and heated at 80° C. for 45 minutes and then allowed to cool. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic phase was washed with water and with brine, dried over MgSO₄, and concentrated to leave a viscous residue. This residue was purified by column chromatography through silica gel eluted with a gradient of ethyl acetate (30% to 100%) in hexane to give the title product, a compound of the present invention, as an off-white solid (209 mg).

¹H NMR δ 7.71 (m, 2H), 6.54 (m, 2H), 3.86 (s, 3H), 2.07 (s, 3H); 400 amu (AP⁺).

Synthesis Example 9 Preparation of 4-[[1,3-Dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzenamine (Compound 371)

5-(2,6-Difluoro-4-nitrophenoxy)-1,3-dimethyl-4-(2,4,6-trifluorophenyl)-1H-pyrazole (i.e. the product of Synthesis Example 8) (0.780 g, 1.95 mmol) was combined with iron powder (325 mesh, 0.58 g, 10 mmol) and ammonium chloride (64 mg, 1.2 mmol) in ethanol (27 mL) to which water (3 mL) had been added. The mixture was heated at reflux for 1.25 h and then allowed to cool. The reaction mixture was diluted with an equal volume of ethyl acetate and filtered through Celite filter aid. The filtrate was dried with MgSO₄ and concentrated. Analysis by LC/MS showed the major component (93%) to have mass 370 amu (AP+). The residue was dissolved in anhydrous dimethyl sulfoxide (8 mL), and a commercial solution of sodium methoxide in methanol (0.45 mL of 25% solution) was added. This solution was stirred under nitrogen and heated at reflux for 1 h. Additional sodium methoxide/methanol solution (0.20 mL) was added, and heating was continued for an additional 30 minutes. The reaction mixture was allowed to cool, and it was then treated with aqueous citric acid solution (1 M, 5 mL), diluted with water (50 mL) and extracted with ethyl acetate (2×25 mL). The organic phase was washed with water (3×) and with brine, dried over MgSO₄, and concentrated to leave the title product, a compound of the present invention, as a viscous oil (0.52 g).

¹H NMR δ 6.29 (m, 2H), 5.95 (m, 2H), 3.80 (s, 3H), 3.75 (s, 3H), 3.55-3.75 (br s, NH₂), 2.01 (s, 3H); 382 amu (AP+).

Synthesis Example 10 Preparation of 5-(4-Chloro-2,6-difluorophenoxy)-4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazole (Compound 58)

Copper(I) chloride (56 mg, 0.42 mmol) was added to a solution of 4-[[4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzenamine (prepared analogous to Synthesis Example 9) (132 mg, 0.346 mmol) in acetonitrile (5 mL). The stirred mixture was cooled using an ice-water bath, and tert-butyl nitrite (90% technical grade, 72 μL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature and stirred at room temperature overnight, and then it was heated at reflux for 1 h. Hydrochloric acid (1 N, 5 mL) was added, and the mixture was extracted with ethyl acetate (˜20 mL). The organic phase was washed with brine, dried over MgSO₄, and concentrated. The residue was purified by column chromatography through silica gel eluted with 20% ethyl acetate in hexane to give the title product, a compound of the present invention, as a viscous oil (45 mg).

¹H NMR δ 6.74 (m, 2H), 6.30 (m, 2H), 3.83 (s, 3H), 3.75 (s, 3H), 2.03 (s, 3H); 401 amu (AP+).

By the procedures described herein together with methods known in the art, the compounds disclosed in the Tables that follow can be prepared. The following abbreviations are used in the Table which follows: Me means methyl, Et means ethyl, n-Pr means n-propyl, c-Pr means cyclopropyl, Ph means phenyl, OMe (or MeO) means methoxy, OEt (or EtO) means ethoxy, —CN means cyano, and —NO₂ means nitro.

TABLE 1

Q¹ is 2,6-di-F-Ph, and R² is Me. (R³)_(p) 2-F 3-F 4-F 2-Cl 3-Cl 4-Cl 2-Br 3-Br 4-Br 2,4-di-F 2,6-di-F 2,4,6-tri-F 2,4,5-tri-F 2,3,5-tri-F 2,3,6-tri-F 2-Cl-4-F 2-F-4-Cl 2,4-di-Cl 2,6-di-Cl 2,4,6-tri-Cl 2-Br-4-F 2-I-4-F 2-Me-4-F 2-F-4-MeO 2-Cl-4-MeO 2-Br-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-Cl-4-CN 2-Br-4-CN 2,6-di-F-4-CN 2-Cl-4,5-di-F 2-Cl-4,6-di-F 2-Br-4,5-di-F 2-Br-4,6-di-F 4-Cl-2,5-di-F 4-Cl-2,6-di-F 4-Br-2,5-di-F 4-Br-2,6-di-F 2,4-di-Cl-6-F 2,6-di-Cl-4-F 2,6-di-Cl-4-MeO 2-CF₃-4-F 4-Me 2,4-di-Me 2-F-4-Br 2-Cl-4-Br 2-Br-4-Cl 2-Br-4-F-6-Cl 2-Cl-4-Br-6-F

The present disclosure also includes Tables 2 through 84, each of which is constructed the same as Table 1 above, except that the row heading in Table 1 (i.e. “Q¹ is 2,6-di-F-Ph, and R² is Me.”) is replaced with the respective row heading shown below. For Example, in Table 2 the row heading is “Q¹ is 2,6-di-F-Ph, and R² is Cl.”, and (R³)_(p) is as defined in Table 1 above. Thus, the first entry in Table 2 specifically discloses 2-chloro-4-(2,6-difluorophenyl)-N-(2-fluorophenyl)-1-methyl-1H-pyrazol-5-amine. Tables 3 through 84 are constructed similarly.

Table Row Heading 2 Q¹ is 2,6-di-F—Ph, and R² is Cl. 3 Q¹ is 2,6-di-F—Ph, and R² is Br. 4 Q¹ is 2,4-di-F—Ph, and R² is Me. 5 Q¹ is 2,4-di-F—Ph, and R² is Cl. 6 Q¹ is 2,4-di-F—Ph, and R² is Br. 7 Q¹ is 2,4,6-tri-F—Ph, and R² is Me. 8 Q¹ is 2,4,6-tri-F—Ph, and R² is Cl. 9 Q¹ is 2,4,6-tri-F—Ph, and R² is Br. 10 Q¹ is 2,6-di-F-4-OMe—Ph, and R² is Me. 11 Q¹ is 2,6-di-F-4-OMe—Ph, and R² is Cl. 12 Q¹ is 2,6-di-F-4-OMe—Ph, and R² is Br.  12A Q¹ is 2,6-di-F-4-OEt—Ph, and R² is Me.  12B Q¹ is 2,6-di-F-4-OEt—Ph, and R² is Cl.  12C Q¹ is 2,6-di-F-4-OEt—Ph, and R² is Br. 13 Q¹ is 2,6-di-F-4-CN—Ph, and R² is Me. 14 Q¹ is 2,6-di-F-4-CN—Ph, and R² is Cl. 15 Q¹ is 2,6-di-F-4-CN—Ph, and R² is Br. 16 Q¹ is 2-Cl-4-F—Ph, and R² is Me. 17 Q¹ is 2-Cl-4-F—Ph, and R² is Cl. 18 Q¹ is 2-Cl-4-F—Ph, and R² is Br. 19 Q¹ is 2-Cl-6-F—Ph, and R² is Me. 20 Q¹ is 2-Cl-6-F—Ph, and R² is Cl. 21 Q¹ is 2-Cl-6-F-Ph, and R² is Br. 22 Q¹ is 2-Cl-4,6-di-F—Ph, and R² is Me. 23 Q¹ is 2-Cl-4,6-di-F—Ph, and R² is Cl. 24 Q¹ is 2-Cl-4,6-di-F—Ph, and R² is Br. 25 Q¹ is 4-Cl-2,6-di-F—Ph, and R² is Me. 26 Q¹ is 4-Cl-2,6-di-F—Ph, and R² is Cl. 27 Q¹ is 4-Cl-2,6-di-F—Ph, and R² is Br. 28 Q¹ is 2-Br-4-F—Ph, and R² is Me. 29 Q¹ is 2-Br-4-F—Ph, and R² is Cl. 30 Q¹ is 2-Br-4-F—Ph, and R² is Br. 31 Q¹ is 2-Br-6-F—Ph, and R² is Me. 32 Q¹ is 2-Br-6-F—Ph, and R² is Cl. 33 Q¹ is 2-Br-6-F—Ph, and R² is Br. 34 Q¹ is 2-Me-4-F—Ph, and R² is Me. 35 Q¹ is 2-Me-4-F—Ph, and R² is Cl. 36 Q¹ is 2-Me-4-F—Ph, and R² is Br. 37 Q¹ is 2-I-4-F—Ph, and R² is Me. 38 Q¹ is 2-I-4-F—Ph, and R² is Cl. 39 Q¹ is 2-I-4-F—Ph, and R² is Br. 40 Q¹ is 2-F—Ph, and R² is Me. 41 Q¹ is 2-F—Ph, and R² is Cl. 42 Q¹ is 2-F—Ph, and R² is Br. 43 Q¹ is 2-Cl—Ph, and R² is Me. 44 Q¹ is 2-Cl—Ph, and R² is Cl. 45 Q¹ is 2-Cl—Ph, and R² is Br. 46 Q¹ is 2-Br—Ph, and R² is Me. 47 Q¹ is 2-Br—Ph, and R² is Cl. 48 Q¹ is 2-Br—Ph, and R² is Br. 49 Q¹ is 2-F-4-Cl—Ph, and R² is Me. 50 Q¹ is 2-F-4-Cl—Ph, and R² is Cl. 51 Q¹ is 2-F-4-Cl—Ph, and R² is Br. 52 Q¹ is 2,4-di-Cl—Ph, and R² is Me. 53 Q¹ is 2,4-di-Cl—Ph, and R² is Cl. 54 Q¹ is 2,4-di-Cl—Ph, and R² is Br. 55 Q¹ is 2,6-di-Cl—Ph, and R² is Me. 56 Q¹ is 2,6-di-Cl—Ph, and R² is Cl. 57 Q¹ is 2,6-di-Cl—Ph, and R² is Br. 58 Q¹ is 2-F-4-MeO—Ph, and R² is Me. 59 Q¹ is 2-F-4-MeO—Ph, and R² is Cl. 60 Q¹ is 2-F-4-MeO—Ph, and R² is Br.  60A Q¹ is 2-F-4-EtO—Ph, and R² is Me.  60B Q¹ is 2-F-4-EtO—Ph, and R² is Cl.  60C Q¹ is 2-F-4-EtO—Ph, and R² is Br. 61 Q¹ is 2-Cl-4-MeO—Ph, and R² is Me. 62 Q¹ is 2-Cl-4-MeO—Ph, and R² is Cl. 63 Q¹ is 2-Cl-4-MeO—Ph, and R² is Br.  63A Q¹ is 2-Cl-4-EtO—Ph, and R² is Me.  63B Q¹ is 2-Cl-4-EtO—Ph, and R² is Cl.  63C Q¹ is 2-Cl-4-EtO—Ph, and R² is Br. 64 Q¹ is 2-Br-4-MeO—Ph, and R² is Me. 65 Q1 is 2-Br-4-MeO—Ph, and R² is Cl. 66 Q¹ is 2-Br-4-MeO—Ph, and R² is Br.  66A Q¹ is 2-Br-4-EtO—Ph, and R² is Me.  66B Q¹ is 2-Br-4-EtO—Ph, and R² is Cl.  66C Q¹ is 2-Br-4-EtO—Ph, and R² is Br. 67 Q¹ is 2-F-4-CN—Ph, and R² is Me. 68 Q¹ is 2-F-4-CN—Ph, and R² is Cl. 69 Q¹ is 2-F-4-CN—Ph, and R² is Br. 70 Q¹ is 2-Cl-4-CN—Ph, and R² is Me. 71 Q¹ is 2-Cl-4-CN—Ph, and R² is Cl. 72 Q¹ is 2-Cl-4-CN—Ph, and R² is Br. 73 Q¹ is 2-Br-4-CN—Ph, and R² is Me. 74 Q¹ is 2-Br-4-CN—Ph, and R² is Cl. 75 Q¹ is 2-Br-4-CN—Ph, and R² is Br. 76 Q¹ is 2,5-di-Cl-3-pyridinyl, and R² is Me. 77 Q¹ is 2,5-di-Cl-3-pyridinyl, and R² is Cl. 78 Q¹ is 2,5-di-Cl-3-pyridinyl, and R² is Br. 79 Q¹ is 2-Cl-3-thienyl, and R² is Me. 80 Q¹ is 2-Cl-3-thienyl, and R² is Cl. 81 Q¹ is 2-Cl-3-thienyl, and R² is Br. 82 Q¹ is 2,5-di-Cl-3-thienyl, and R² is Me. 83 Q¹ is 2,5-di-Cl-3-thienyl, and R² is Cl. 84 Q¹ is 2,5-di-Cl-3-thienyl, and R² is Br.

TABLE 85

Q¹ is 2,6-di-F-Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. (R³)_(p) 4-F 4-C1 4-Br 2,4-di-F 2-Br-4-F 2,6-di-F 2,4-di-Cl 2,6-di-Cl 2-Cl-4-F 2-F-4-Cl 2-F-4-Br 2-Br-6-F 2-Cl-4-Br 2-Br-4-Cl 2-I-4-F 2-F-4-I 2-Cl-4,6-di-F 4-Cl-2,6-di-F 2-Br-4,6-di-F 4-Br-2,6-di-F 2-F-4-MeO 2-Cl-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-C1-4-CN 2-Br-4-CN 2,6-di-F-4-CN 2-F-4-NO₂ 2-Cl-4-NO₂ 2-Br-4-NO₂ 2,5-di-F-4-CN 4-Cl-2,5-di-F 2-Br-4,5-di-F 4-Br-2,5-di-F 2-Cl-4,5-di-F

The present disclosure also includes Tables 86 through 280, each of which is constructed the same as Table 85 above, except that the row heading in Table 85 (i.e. “Q¹ is 2,6-di-F-Ph, X is O, R¹ and R^(1a) are both H, and R² is Me.”) is replaced with the respective row heading shown below. For Example, in Table 86 the row heading is “Q¹ is 2,6-di-F-Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl.” and (R³)_(p) is as defined in Table 85 above. Thus, the first entry in Table 86 specifically discloses 3-chloro-4-(2,6-difluorophenyl)-5-(4-fluorophenoxy)-1-methyl-1H-pyrazole. Tables 87 through 280 are constructed similarly.

Table Row Heading 86 Q¹ is 2,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 87 Q¹ is 2,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 88 Q¹ is 2,4-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 89 Q¹ is 2,4-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 90 Q¹ is 2,4-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 91 Q¹ is 2,4,6-tri-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 92 Q¹ is 2,4,6-tri-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 93 Q¹ is 2,4,6-tri-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 94 Q¹ is 2,6-di-F-4-OMe—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 95 Q¹ is 2,6-di-F-4-OMe—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 96 Q¹ is 2,6-di-F-4-OMe—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br.   96A Q¹ is 2,6-di-F-4-OEt—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me.   96B Q¹ is 2,6-di-F-4-OEt—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl.   96C Q¹ is 2,6-di-F-4-OEt—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 97 Q¹ is 2,6-di-F-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 98 Q¹ is 2,6-di-F-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 99 Q¹ is 2,6-di-F-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 100 Q¹ is 2-Cl-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 101 Q¹ is 2-Cl-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 102 Q¹ is 2-Cl-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 103 Q¹ is 2-Cl-6-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 104 Q¹ is 2-Cl-6-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 105 Q¹ is 2-Cl-6-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 106 Q¹ is 2-Cl-4,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 107 Q¹ is 2-Cl-4,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 108 Q¹ is 2-Cl-4,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 109 Q¹ is 4-Cl-2,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 110 Q¹ is 4-Cl-2,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 111 Q¹ is 4-Cl-2,6-di-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 112 Q¹ is 2-Br-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 113 Q¹ is 2-Br-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 114 Q¹ is 2-Br-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 115 Q¹ is 2-Br-6-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 116 Q¹ is 2-Br-6-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 117 Q¹ is 2-Br-6-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 118 Q¹ is 2-Me-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 119 Q¹ is 2-Me-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 120 Q¹ is 2-Me-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 121 Q¹ is 2-I-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 122 Q¹ is 2-I-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 123 Q¹ is 2-I-4-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 124 Q¹ is 2-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 125 Q¹ is 2-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 126 Q¹ is 2-F—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 127 Q¹ is 2-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 128 Q¹ is 2-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 129 Q¹ is 2-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 130 Q¹ is 2-Br—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 131 Q¹ is 2-Br—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 132 Q¹ is 2-Br—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 133 Q¹ is 2-F-4-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 134 Q¹ is 2-F-4-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 135 Q¹ is 2-F-4-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 136 Q¹ is 2,4-di-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 137 Q¹ is2,4-di-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 138 Q¹ is 2,4-di-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 139 Q¹ is 2,6-di-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 140 Q¹ is 2,6-di-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 141 Q¹ is 2,6-di-Cl—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 142 Q¹ is 2-F-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 143 Q¹ is 2-F-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 144 Q¹ is 2-F-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br.  144A Q¹ is 2-F-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me.  144B Q¹ is 2-F-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl.  144C Q¹ is 2-F-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 145 Q¹ is 2-Cl-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 146 Q¹ is 2-Cl-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 147 Q¹ is 2-Cl-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br.  147A Q¹ is 2-Cl-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me.  147B Q¹ is 2-Cl-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl.  147C Q¹ is 2-Cl-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 148 Q¹ is 2-Br-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 149 Q¹ is 2-Br-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 150 Q¹ is 2-Br-4-MeO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br.  150A Q¹ is 2-Br-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me.  150B Q¹ is 2-Br-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl.  150C Q¹ is 2-Br-4-EtO—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 151 Q¹ is 2-F-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 152 Q¹ is 2-F-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 153 Q¹ is 2-F-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 154 Q¹ is 2-Cl-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 155 Q¹ is 2-Cl-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 156 Q¹ is 2-Cl-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 157 Q¹ is 2-Br-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Me. 158 Q¹ is 2-Br-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Cl. 159 Q¹ is 2-Br-4-CN—Ph, X is O, R¹ and R^(1a) are both H, and R² is Br. 160 Q¹ is 2,5-di-Cl-3-pyridinyl, X is O, R¹ and R^(1a) are both H, and R² is Me. 161 Q¹ is 2,5-di-Cl-3-pyridinyl, X is O, R¹ and R^(1a) are both H, and R² is Cl. 162 Q¹ is 2,5-di-Cl-3-pyridinyl, X is O, R¹ and R^(1a) are both H, and R² is Br. 163 Q¹ is 2-Cl-3-thienyl, X is O, R¹ and R^(1a) are both H, and R² is Me. 164 Q¹ is 2-Cl-3-thienyl, X is O, R¹ and R^(1a) are both H, and R² is Cl. 165 Q¹ is 2-Cl-3-thienyl, X is O, R¹ and R^(1a) are both H, and R² is Br. 166 Q¹ is 2,5-di-Cl-3-thienyl, X is O, R¹ and R^(1a) are both H, and R² is Me. 167 Q¹ is 2,5-di-Cl-3-thienyl, X is O, R¹ and R^(1a) are both H, and R² is Cl. 168 Q¹ is 2,5-di-Cl-3-thienyl, X is O, R¹ and R^(1a) are both H, and R² is Br. 169 Q¹ is 2,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 170 Q¹ is 2,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 171 Q¹ is 2,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 172 Q¹ is 2,4-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 173 Q¹ is 2,4-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 174 Q¹ is 2,4-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 175 Q¹ is 2,4,6-tri-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 176 Q¹ is 2,4,6-tri-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 177 Q¹ is 2,4,6-tri-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 178 Q¹ is 2,6-di-F-4-OMe—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 179 Q¹ is 2,6-di-F-4-OMe—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 180 Q¹ is 2,6-di-F-4-OMe—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br.  180A Q¹ is 2,6-di-F-4-OEt—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me.  180B Q¹ is 2,6-di-F-4-OEt—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl.  180C Q¹ is 2,6-di-F-4-OEt—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 181 Q¹ is 2,6-di-F-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 182 Q¹ is 2,6-di-F-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 183 Q¹ is 2,6-di-F-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 184 Q¹ is 2-Cl-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 185 Q¹ is 2-Cl-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 186 Q¹ is 2-Cl-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 187 Q¹ is 2-Cl-6-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 188 Q¹ is 2-Cl-6-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 189 Q¹ is 2-Cl-6-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 190 Q¹ is 2-Cl-4,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 191 Q¹ is 2-Cl-4,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 192 Q¹ is 2-Cl-4,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 193 Q¹ is 4-Cl-2,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 194 Q¹ is 4-Cl-2,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 195 Q¹ is 4-Cl-2,6-di-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 196 Q¹ is 2-Br-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 197 Q¹ is 2-Br-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 198 Q¹ is 2-Br-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 199 Q¹ is 2-Br-6-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 200 Q¹ is 2-Br-6-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 201 Q¹ is 2-Br-6-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 202 Q¹ is 2-Me-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 203 Q¹ is 2-Me-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 204 Q¹ is 2-Me-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 205 Q¹ is 2-I-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 206 Q¹ is 2-I-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 207 Q¹ is 2-I-4-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 208 Q¹ is 2-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 209 Q¹ is 2-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 210 Q¹ is 2-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 211 Q¹ is 2-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 212 Q¹ is 2-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 213 Q¹ is 2-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 214 Q¹ is 2-Br—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 215 Q¹ is 2-Br—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 216 Q¹ is 2-Br—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 217 Q¹ is 2-F-4-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 218 Q¹ is 2-F-4-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 219 Q¹ is 2-F-4-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 220 Q¹ is 2,4-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 221 Q¹ is 2,4-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 222 Q¹ is 2,4-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 223 Q¹ is 2,6-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 224 Q¹ is 2,6-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 225 Q¹ is 2,6-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 226 Q¹ is 2-F-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 227 Q¹ is 2-F-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 228 Q¹ is 2-F-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br.  228A Q¹ is 2-F-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me.  228B Q¹ is 2-F-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl.  228C Q¹ is 2-F-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 229 Q¹ is 2-Cl-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 230 Q¹ is 2-Cl-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 231 Q¹ is 2-Cl-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br.  231A Q¹ is 2-Cl-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me.  231B Q¹ is 2-Cl-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl.  231C Q¹ is 2-Cl-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 232 Q¹ is 2-Br-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 233 Q¹ is 2-Br-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 234 Q¹ is 2-Br-4-MeO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br.  234A Q¹ is 2-Br-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me.  234B Q¹ is 2-Br-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl.  234C Q¹ is 2-Br-4-EtO—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 235 Q¹ is 2-F-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 236 Q¹ is 2-F-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 237 Q¹ is 2-F-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 238 Q¹ is 2-Cl-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 239 Q¹ is 2-Cl-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 240 Q¹ is 2-Cl-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 241 Q¹ is 2-Br-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Me. 242 Q¹ is 2-Br-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Cl. 243 Q¹ is 2-Br-4-CN—Ph, X is S, R¹ and R^(1a) are both H, and R² is Br. 244 Q¹ is 2,5-di-Cl-3-pyridinyl, X is S, R¹ and R^(1a) are both H, and R² is Me. 245 Q¹ is 2,5-di-Cl-3-pyridinyl, X is S, R¹ and R^(1a) are both H, and R² is Cl. 246 Q¹ is 2,5-di-Cl-3-pyridinyl, X is S, R¹ and R^(1a) are both H, and R² is Br. 247 Q¹ is 2-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Me. 248 Q¹ is 2-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Cl. 249 Q¹ is 2-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Br. 250 Q¹ is 2,5-di-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Me. 251 Q¹ is 2,5-di-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Cl. 252 Q¹ is 2,5-di-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Br. 253 Q¹ is 2,6-di-F—Ph, X is NH, R¹ and R^(1a) form c-Pr, and R² is Me. 254 Q¹ is is 2,4-di-F—Ph, X is O, R¹ is Et, R^(1a) is H, and R² is Cl. 255 Q¹ is is 2,4,6-tri-F—Ph, X is S, R¹ and R^(1a) are both H, and R² is Et. 256 Q¹ is is 2,6-di-F-4-OMe—Ph, X is CHOH, R¹ 257 Q¹ is is 2,6-di-F-4-CN—Ph, X is NH, R¹ is CH═CH2, R^(1a) is H, and R² is Cl. 258 Q¹ is 2-Cl-4-F—Ph, X is CHOH, X is O, R¹ is c-Pr, R^(1a) is H, and R² is Br. 259 Q¹ is 2-Cl-6-F—Ph, X is S, R¹ and R^(1a) form c-Pr, and R² is Me. 260 Q¹ is 2-Cl-4,6-di-F—Ph, X is CHOH, R¹ is c-Pr, R^(1a) is H, and R² is Cl. 261 Q¹ is 4-Cl-2,6-di-F—Ph, X is NH, X is NH, R¹ is Et, R^(1a) is H, and R² is Br. 262 Q¹ is 2-Br-4-F—Ph, X is O, R¹ and R^(1a) both H, and R² is Et. 263 Q¹ is 2-Br-6-F—Ph, X is S, R¹ is CH₂CH═CH₂, R^(1a) is H, and R² is Cl. 264 Q¹ is 2-Me-4-F—Ph, X is CHOH, R¹ and R^(1a) are both H, and R ² is c-Pr. 265 Q¹ is 2-1-4-F—Ph, X is NH, R¹ is CH₂CF₃, R^(1a) is H, and R² is Me. 266 Q¹ is 2-F—Ph, X is O, R¹ is CH₂F, R^(1a) is H, and R² is Cl. 267 Q¹ is 2-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is CH₂Cl. 268 Q¹ is 2-Br—Ph, X is CHCH₃, R¹ and R^(1a) are both H, and R² is Me. 269 Q¹ is 2-F-4-Cl—Ph, X is C(CH₃)OH, R¹ and R^(1a) are both H, and R² is Me. 270 Q¹ is 2,4-di-Cl—Ph, X is O, R¹ is Et, R^(1a) is H, and R² is Br. 271 Q¹ is 2,6-di-Cl—Ph, X is S, R¹ and R^(1a) are both H, and R² is OMe. 272 Q¹ is 2-F-4-MeO—Ph, X is CHOCH₃, R¹ and R^(1a) are both H, and R² is Cl. 273 Q¹ is 2-Cl-4-MeO—Ph, X is NH, R¹ and R^(1a) form c-Pr, and R² is Br. 274 Q¹ is 2-Br-4-MeO—Ph, X is O, R¹ is n-Pr, R^(1a) is H, and R² is Me. 275 Q¹ is 2-F-4-CN—Ph, X is NH, R¹ is CH₂CCH, R^(1a) is H, and R² is Cl. 276 Q¹ is 2-Cl-4-CN—Ph, X is C(OCH₃)₂, R¹ and R^(1a) are both H, and R² is Br. 277 Q¹ is 2-Br-4-CN—Ph, X is NH, R¹ and R^(1a) form c-Pr, and R² is Me. 278 Q¹ is 2,5-di-Cl-3-pyridinyl, X is O, R¹ is c-Pr, R^(1a) is H, and R² is Cl. 279 Q¹ is 2-Cl-3-thienyl, X is S, R¹ and R^(1a) are both H, and R² is Et. 280 Q¹ is 2,5-di-Cl-3-thienyl, X is CHOH, R¹ is Et, R^(1a) is H, and R² is Me.

TABLE 281

Q¹ is 2,6-di-F-Ph, X is CHOH, and R² is Me. (R³)_(p) 4-F 4-Cl 4-Br 4-Me 2,4-di-F 2,6-di-F 2,4-di-Cl 2,6-di-Cl 2-Cl-4-F 2-F-4-Cl 2-F-4-Br 2-Br-6-F 2-Cl-4-Br 2-Br-4-Cl 2-I-4-F 2-F-4-I 2-Cl-4,6-di-F 4-Cl-2,6-di-F 2-Br-4,6-di-F 4-Br-2,6-di-F 2-Br-4-F 2-Me-4-F 2,4,6-tri-F 2-Cl-4,5-di-F 4-Cl-2,5-di-F 2-F-4-CN 2-C1-4-CN 2-Br-4-CN 2,6-diF-4-CN 2-F-4-MeO 2-Cl-4-MeO 2-Br-4-MeO 2,6-di-F-4-MeO 4-Br-2,5-di-F 2-Br-4,5-di-F

The present disclosure also includes Tables 282 through 448, each of which is constructed the same as Table 281 above, except that the row heading in Table 281 (i.e. “Q¹ is 2,6-di-F-Ph, X is CHOH, and R² is Me.”) is replaced with the respective row heading shown below. For Example, in Table 282 the row heading is “Q¹ is 2,6-di-F-Ph, X is CHOH, and R² is Cl.” and (R³)_(p) is as defined in Table 281 above. Thus, the first entry in Table 282 specifically discloses 3-chloro-4-(2,6-difluorophenyl)-α-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-methanol. Tables 283 through 448 are constructed similarly.

Table Row Heading 282 Q¹ is 2,6-di-F—Ph, X is CHOH, and R² is Cl. 283 Q¹ is 2,6-di-F—Ph, X is CHOH, and R² is Br. 284 Q¹ is 2,4-di-F—Ph, X is CHOH, and R² is Me. 285 Q¹ is 2,4-di-F—Ph, X is CHOH, and R² is Cl. 286 Q¹ is 2,4-di-F—Ph, X is CHOH, and R² is Br. 287 Q¹ is 2,4,6-tri-F—Ph, X is CHOH, and R² is Me. 288 Q¹ is 2,4,6-tri-F—Ph, X is CHOH, and R² is Cl. 289 Q¹ is 2,4,6-tri-F—Ph, X is CHOH, and R² is Br. 290 Q¹ is 2,6-di-F-4-OMe—Ph, X is CHOH, and R² is Me. 291 Q¹ is 2,6-di-F-4-OMe—Ph, X is CHOH, and R² is Cl. 292 Q¹ is 2,6-di-F-4-OMe—Ph, X is CHOH, and R² is Br.  292A Q¹ is 2,6-di-F-4-OEt—Ph, X is CHOH, and R² is Me.  292B Q¹ is 2,6-di-F-4-OEt—Ph, X is CHOH, and R² is Cl.  292C Q¹ is 2,6-di-F-4-OEt—Ph, X is CHOH, and R² is Br. 293 Q¹ is 2,6-di-F-4-CN—Ph, X is CHOH, and R² is Me. 294 Q¹ is 2,6-di-F-4-CN—Ph, X is CHOH, and R² is Cl. 295 Q¹ is 2,6-di-F-4-CN—Ph, X is CHOH, and R² is Br. 296 Q¹ is 2-Cl-4-F—Ph, X is CHOH, and R² is Me. 297 Q¹ is 2-Cl-4-F—Ph, X is CHOH, and R² is Cl. 298 Q¹ is 2-Cl-4-F—Ph, X is CHOH, and R² is Br. 299 Q¹ is 2-Cl-6-F—Ph, X is CHOH, and R² is Me. 300 Q¹ is 2-Cl-6-F—Ph, X is CHOH, and R² is Cl. 301 Q¹ is 2-Cl-6-F—Ph, X is CHOH, and R² is Br. 302 Q¹ is 2-Cl-4,6-di-F—Ph, X is CHOH, and R² is Me. 303 Q¹ is 2-Cl-4,6-di-F—Ph, X is CHOH, and R² is Cl. 304 Q¹ is 2-Cl-4,6-di-F—Ph, X is CHOH, and R² is Br. 305 Q¹ is 4-Cl-2,6-di-F—Ph, X is CHOH, and R² is Me. 306 Q¹ is 4-Cl-2,6-di-F—Ph, X is CHOH, and R² is Cl. 307 Q¹ is 4-Cl-2,6-di-F—Ph, X is CHOH, and R² is Br. 308 Q¹ is 2-Br-4-F—Ph, X is CHOH, and R² is Me. 309 Q¹ is 2-Br-4-F—Ph, X is CHOH, and R² is Cl. 310 Q¹ is 2-Br-4-F—Ph, X is CHOH, and R² is Br. 311 Q¹ is 2-Br-6-F—Ph, X is CHOH, and R² is Me. 312 Q¹ is 2-Br-6-F—Ph, X is CHOH, and R² is Cl. 313 Q¹ is 2-Br-6-F—Ph, X is CHOH, and R² is Br. 314 Q¹ is 2-Me-4-F—Ph, X is CHOH, and R² is Me. 315 Q¹ is 2-Me-4-F—Ph, X is CHOH, and R² is Cl. 316 Q¹ is 2-Me-4-F—Ph, X is CHOH, and R² is Br. 317 Q¹ is 2-1-4-F—Ph, X is CHOH, and R² is Me. 318 Q¹ is 2-1-4-F—Ph, X is CHOH, and R² is Cl. 319 Q¹ is 2-1-4-F—Ph, X is CHOH, and R² is Br. 320 Q¹ is 2-F—Ph, X is CHOH, and R² is Me. 321 Q¹ is 2-F—Ph, X is CHOH, and R² is Cl. 322 Q¹ is 2-F—Ph, X is CHOH, and R² is Br. 323 Q¹ is 2-Cl—Ph, X is CHOH, and R² is Me. 324 Q¹ is 2-Cl—Ph, X is CHOH, and R² is Cl. 325 Q¹ is 2-Cl—Ph, X is CHOH, and R² is Br. 326 Q¹ is 2-Br—Ph, X is CHOH, and R² is Me. 327 Q¹ is 2-Br—Ph, X is CHOH, and R² is Cl. 328 Q¹ is 2-Br—Ph, X is CHOH, and R² is Br. 329 Q¹ is 2-F-4-Cl—Ph, X is CHOH, and R² is Me. 330 Q¹ is 2-F-4-Cl—Ph, X is CHOH, and R² is Cl. 331 Q¹ is 2-F-4-Cl—Ph, X is CHOH, and R² is Br. 332 Q¹ is 2,4-di-Cl—Ph, X is CHOH, and R² is Me. 333 Q¹ is 2,4-di-Cl—Ph, X is CHOH, and R² is Cl. 334 Q¹ is 2,4-di-Cl—Ph, X is CHOH, and R² is Br. 335 Q¹ is 2,6-di-Cl—Ph, X is CHOH, and R² is Me. 336 Q¹ is 2,6-di-Cl—Ph, X is CHOH, and R² is Cl. 337 Q¹ is 2,6-di-Cl—Ph, X is CHOH, and R² is Br. 338 Q¹ is 2-F-4-MeO—Ph, X is CHOH, and R² is Me. 339 Q¹ is 2-F-4-MeO—Ph, X is CHOH, and R² is Cl. 340 Q¹ is 2-F-4-MeO—Ph, X is CHOH, and R² is Br.  340A Q¹ is 2-F-4-EtO—Ph, X is CHOH, and R² is Me.  340B Q¹ is 2-F-4-EtO—Ph, X is CHOH, and R² is Cl.  340C Q¹ is 2-F-4-EtO—Ph, X is CHOH, and R² is Br. 341 Q¹ is 2-Cl-4-MeO—Ph, X is CHOH, and R² is Me. 342 Q¹ is 2-Cl-4-MeO—Ph, X is CHOH, and R² is Cl. 343 Q¹ is 2-Cl-4-MeO—Ph, X is CHOH, and R² is Br.  343A Q¹ is 2-Cl-4-EtO—Ph, X is CHOH, and R² is Me.  343B Q¹ is 2-Cl-4-EtO—Ph, X is CHOH, and R² is Cl.  343C Q¹ is 2-Cl-4-EtO—Ph, X is CHOH, and R² is Br. 344 Q¹ is 2-Br-4-MeO—Ph, X is CHOH, and R² is Me. 345 Q¹ is 2-Br-4-MeO—Ph, X is CHOH, and R² is Cl. 346 Q¹ is 2-Br-4-MeO—Ph, X is CHOH, and R² is Br.  346A Q¹ is 2-Br-4-EtO—Ph, X is CHOH, and R² is Me.  346B Q¹ is 2-Br-4-EtO—Ph, X is CHOH, and R² is Cl.  346C Q¹ is 2-Br-4-EtO—Ph, X is CHOH, and R² is Br. 347 Q¹ is 2-F-4-CN—Ph, X is CHOH, and R² is Me. 348 Q¹ is 2-F-4-CN—Ph, X is CHOH, and R² is Cl. 349 Q¹ is 2-F-4-CN—Ph, X is CHOH, and R² is Br. 350 Q¹ is 2-Cl-4-CN—Ph, X is CHOH, and R² is Me. 351 Q¹ is 2-Cl-4-CN—Ph, X is CHOH, and R² is Cl. 352 Q¹ is 2-Cl-4-CN—Ph, X is CHOH, and R² is Br. 353 Q¹ is 2-Br-4-CN—Ph, X is CHOH, and R² is Me. 354 Q¹ is 2-Br-4-CN—Ph, X is CHOH, and R² is Cl. 355 Q¹ is 2-Br-4-CN—Ph, X is CHOH, and R² is Br. 356 Q¹ is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R² is Me. 357 Q¹ is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R² is Cl. 358 Q¹ is 2,5-di-Cl-3-pyridinyl, X is CHOH, and R² is Br. 359 Q¹ is 2-Cl-3-thienyl, X is CHOH, and R² is Me. 360 Q¹ is 2-Cl-3-thienyl, X is CHOH, and R² is Cl. 361 Q¹ is 2-Cl-3-thienyl, X is CHOH, and R² is Br. 362 Q¹ is 2,5-di-Cl-3-thienyl, X is CHOH, and R² is Me. 363 Q¹ is 2,5-di-Cl-3-thienyl, X is CHOH, and R² is Cl. 364 Q¹ is 2,5-di-Cl-3-thienyl, X is CHOH, and R² is Br. 365 Q¹ is 2,6-di-F—Ph, X is C(O), and R² is Cl. 366 Q¹ is 2,6-di-F—Ph, X is C(O), and R² is Cl. 367 Q¹ is 2,6-di-F—Ph, X is C(O), and R² is Br. 368 Q¹ is 2,4-di-F—Ph, X is C(O), and R² is Me. 369 Q¹ is 2,4-di-F—Ph, X is C(O), and R² is Cl. 370 Q¹ is 2,4-di-F—Ph, X is C(O), and R² is Br. 371 Q¹ is 2,4,6-tri-F—Ph, X is C(O), and R² is Me. 372 Q¹ is 2,4,6-tri-F—Ph, X is C(O), and R² is Cl. 373 Q¹ is 2,4,6-tri-F—Ph, X is C(O), and R² is Br. 374 Q¹ is 2,6-di-F-4-OMe—Ph, X is C(O), and R² is Me. 375 Q¹ is 2,6-di-F-4-OMe—Ph, X is C(O), and R² is Cl. 376 Q¹ is 2,6-di-F-4-OMe—Ph, X is C(O), and R² is Br.  376A Q¹ is 2,6-di-F-4-OEt—Ph, X is C(O), and R² is Me.  376B Q¹ is 2,6-di-F-4-OEt—Ph, X is C(O), and R² is Cl.  376C Q¹ is 2,6-di-F-4-OEt—Ph, X is C(O), and R² is Br. 377 Q¹ is 2,6-di-F-4-CN—Ph, X is C(O), and R² is Me. 378 Q¹ is 2,6-di-F-4-CN—Ph, X is C(O), and R² is Cl. 379 Q¹ is 2,6-di-F-4-CN—Ph, X is C(O), and R² is Br. 380 Q¹ is 2-Cl-4-F—Ph, X is C(O), and R² is Me. 381 Q¹ is 2-Cl-4-F—Ph, X is C(O), and R² is Cl. 382 Q¹ is 2-Cl-4-F—Ph, X is C(O), and R² is Br. 383 Q¹ is 2-Cl-6-F—Ph, X is C(O), and R² is Me. 384 Q¹ is 2-Cl-6-F—Ph, X is C(O), and R² is Cl. 385 Q¹ is 2-Cl-6-F—Ph, X is C(O), and R² is Br. 386 Q¹ is 2-Cl-4,6-di-F—Ph, X is C(O), and R² is Me. 387 Q¹ is 2-Cl-4,6-di-F—Ph, X is C(O), and R² is Cl. 388 Q¹ is 2-Cl-4,6-di-F—Ph, X is C(O), and R² is Br. 389 Q¹ is 4-Cl-2,6-di-F—Ph, X is C(O), and R² is Me. 390 Q¹ is 4-Cl-2,6-di-F—Ph, X is C(O), and R² is Cl. 391 Q¹ is 4-Cl-2,6-di-F—Ph, X is C(O), and R² is Br. 392 Q¹ is 2-Br-4-F—Ph, X is C(O), and R² is Me. 393 Q¹ is 2-Br-4-F—Ph, X is C(O), and R² is Cl. 394 Q¹ is 2-Br-4-F—Ph, X is C(O), and R² is Br. 395 Q¹ is 2-Br-6-F—Ph, X is C(O), and R² is Me. 396 Q¹ is 2-Br-6-F—Ph, X is C(O), and R² is Cl. 397 Q¹ is 2-Br-6-F—Ph, X is C(O), and R² is Br. 398 Q¹ is 2-Me-4-F—Ph, X is C(O), and R² is Me. 399 Q¹ is 2-Me-4-F—Ph, X is C(O), and R² is Cl. 400 Q¹ is 2-Me-4-F—Ph, X is C(O), and R² is Br. 401 Q¹ is 2-I-4-F—Ph, X is C(O), and R² is Me. 402 Q¹ is 2-I-4-F—Ph-Ph, X is C(O), and R² is Cl. 403 Q¹ is 2-I-4-F—Ph, X is C(O), and R² is Br. 404 Q¹ is 2-F—Ph, X is C(O), and R² is Me. 405 Q¹ is 2-F—Ph, X is C(O), and R² is Cl. 406 Q¹ is 2-F—Ph, X is C(O), and R² is Br. 407 Q¹ is 2-Cl—Ph, X is C(O), and R² is Me. 408 Q¹ is 2-Cl—Ph, X is C(O), and R² is Cl. 409 Q¹ is 2-Cl—Ph, X is C(O), and R² is Br. 410 Q¹ is 2-Br—Ph, X is C(O), and R² is Me. 411 Q¹ is 2-Br—Ph, X is C(O), and R² is Cl. 412 Q¹ is 2-Br—Ph, X is C(O), and R² is Br. 413 Q¹ is 2-F-4-Cl—Ph, X is C(O), and R² is Me. 414 Q¹ is 2-F-4-Cl—Ph, X is C(O), and R² is Cl. 415 Q¹ is 2-F-4-Cl—Ph, X is C(O), and R² is Br. 416 Q¹ is 2,4-di-Cl—Ph, X is C(O), and R² is Me. 417 Q¹ is 2,4-di-Cl—Ph, X is C(O), and R² is Cl. 418 Q¹ is 2,4-di-Cl—Ph, X is C(O), and R² is Br. 419 Q¹ is 2,6-di-Cl—Ph, X is C(O), and R² is Me. 420 Q¹ is 2,6-di-Cl—Ph, X is C(O), and R² is Cl. 421 Q¹ is 2,6-di-Cl—Ph, X is C(O), and R² is Br. 422 Q¹ is 2-F-4-MeO—Ph, X is C(O), and R² is Me. 423 Q¹ is 2-F-4-MeO—Ph, X is C(O), and R² is Cl. 424 Q¹ is 2-F-4-MeO—Ph, X is C(O), and R² is Br.  424A Q¹ is 2-F-4-EtO—Ph, X is C(O), and R² is Me.  424B Q¹ is 2-F-4-EtO—Ph, X is C(O), and R² is Cl.  424C Q¹ is 2-F-4-EtO—Ph, X is C(O), and R² is Br. 425 Q¹ is 2-Cl-4-MeO—Ph, X is C(O), and R² is Me. 426 Q¹ is 2-Cl-4-MeO—Ph, X is C(O), and R² is Cl. 427 Q¹ is 2-Cl-4-MeO—Ph, X is C(O), and R² is Br.  427A Q¹ is 2-Cl-4-EtO—Ph, X is C(O), and R² is Me.  427B Q¹ is 2-Cl-4-EtO—Ph, X is C(O), and R² is Cl.  427C Q¹ is 2-Cl-4-EtO—Ph, X is C(O), and R² is Br. 428 Q¹ is 2-Br-4-MeO—Ph, X is C(O), and R² is Me. 429 Q¹ is 2-Br-4-MeO—Ph, X is C(O), and R² is Cl. 430 Q¹ is 2-Br-4-MeO—Ph, X is C(O), and R² is Br.  430A Q¹ is 2-Br-4-EtO—Ph, X is C(O), and R² is Me.  430B Q¹ is 2-Br-4-EtO—Ph, X is C(O), and R² is Cl.  430C Q¹ is 2-Br-4-EtO—Ph, X is C(O), and R² is Br. 431 Q¹ is 2-F-4-CN—Ph, X is C(O), and R² is Me. 432 Q¹ is 2-F-4-CN—Ph, X is C(O), and R² is Cl. 433 Q¹ is 2-F-4-CN—Ph, X is C(O), and R² is Br. 434 Q¹ is 2-Cl-4-CN—Ph, X is C(O), and R² is Me. 435 Q¹ is 2-Cl-4-CN—Ph, X is C(O), and R² is Cl. 436 Q¹ is 2-Cl-4-CN—Ph, X is C(O), and R² is Br. 437 Q¹ is 2-Br-4-CN—Ph, X is C(O), and R² is Me. 438 Q¹ is 2-Br-4-CN—Ph, X is C(O), and R² is Cl. 439 Q¹ is 2-Br-4-CN—Ph, X is C(O), and R² is Br. 440 Q¹ is 2,5-di-Cl-3-pyridinyl, X is C(O), and R² is Me. 441 Q¹ is 2,5-di-Cl-3-pyridinyl, X is C(O), and R² is Cl. 442 Q¹ is 2,5-di-Cl-3-pyridinyl, X is C(O), and R² is Br. 443 Q¹ is 2-Cl-3-thienyl, X is C(O), and R² is Me. 444 Q¹ is 2-Cl-3-thienyl, X is C(O), and R² is Cl. 445 Q¹ is 2-Cl-3-thienyl, X is C(O), and R² is Br. 446 Q¹ is 2,5-di-Cl-3-thienyl, X is C(O), and R² is Me. 447 Q¹ is 2,5-di-Cl-3-thienyl, X is C(O), and R² is Cl. 448 Q¹ is 2,5-di-Cl-3-thienyl, X is C(O), and R² is Br.

TABLE 449

Q² Q² Q² Q² 2-Cl-3-pyridinyl 6-Cl-3-pyridinyl 2,6-di-Cl-3-pyridinyl 3-Cl-2-pyridinyl 3,5-di-Cl-2-pyridinyl 3,5-di-F-2-pyridinyl 5-Me-2-pyridinyl 5-CN-2-pyridinyl 5-pyrimidinyl 2-Cl-5-pyrimidinyl 1,3-di-Me-5-pyrazolyl 5-Me-2-thiazolyl 5-Cl-2-pyridinyl 3,5-di-Cl-4-pyridinyl tetrahydro-2H-pyran-4-yl quinolin-2-yl Q¹ is 2,6-di-F—Ph, and X is NH.

The present disclosure also includes Tables 450 through 587, each of which is constructed the same as Table 449 above, except that the row heading in Table 449 (i.e. “Q¹ is 2,6-di-F-Ph, and X is NH.”) is replaced with the respective row heading shown below. For Example, in Table 450 the row heading is “Q¹ is 2,4-di-F-Ph, and X is NH.” and Q² is as defined in Table 449 above. Thus, the first entry in Table 450 specifically discloses 2-chloro-N-[4-(2,4-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]-3-pyridinamine. Tables 451 through 587 are constructed similarly.

Table Row Heading 450 Q¹ is 2,4-di-F-Ph, and X is NH. 451 Q¹ is 2,4,6-tri-F-Ph, and X is NH. 452 Q¹ is 2,6-di-F-4-OMe-Ph, and X is NH. 453 Q¹ is 2,6-di-F-4-CN-Ph, and X is NH. 454 Q¹ is 2-Cl-4-F-Ph, and X is NH. 455 Q¹ is 2-Cl-6-F-Ph, and X is NH. 456 Q¹ is 2-Cl-4,6-di-F-Ph, and X is NH. 457 Q¹ is 4-Cl-2,6-di-F-Ph, and X is NH. 458 Q¹ is 2-Br-4-F-Ph, and X is NH. 459 Q¹ is 2-Br-6-F-Ph, and X is NH. 460 Q¹ is 2-Me-4-F-Ph, and X is NH. 461 Q¹ is 2-I-4-F-Ph, and X is NH. 462 Q¹ is 2-F-Ph, and X is NH. 463 Q¹ is 2-Cl-Ph, and X is NH. 464 Q¹ is 2-Br-Ph, and X is NH. 465 Q¹ is 2-F-4-Cl-Ph, and X is NH. 466 Q¹ is 2,4-di-Cl-Ph, and X is NH. 467 Q¹ is 2,6-di-Cl-Ph, and X is NH. 468 Q¹ is 2-F-4-MeO-Ph, and X is NH. 469 Q¹ is 2-Cl-4-MeO-Ph, and X is NH. 470 Q¹ is 2-Br-4-MeO-Ph, and X is NH. 471 Q¹ is 2-F-4-CN-Ph, and X is NH. 472 Q¹ is 2-Cl-4-CN-Ph, and X is NH. 473 Q¹1 is 2-Br-4-CN-Ph, and X is NH. 474 Q¹ is 2,5-di-Cl-3-pyridinyl, and X is NH. 475 Q¹ is 2-Cl-3-thienyl, and X is NH. 476 Q¹ is 2,5-di-Cl-3-thienyl, and X is NH. 477 Q¹ is 2,6-di-F-Ph, and X is O. 478 Q¹ is 2,4-di-F-Ph, and X is O. 479 Q¹ is 2,4,6-tri-F-Ph, and X is O. 480 Q¹ is 2,6-di-F-4-OMe-Ph, and X is O. 481 Q¹ is 2,6-di-F-4-CN-Ph, and X is O. 482 Q¹ is 2-Cl-4-F-Ph, and X is O. 483 Q¹ is 2-Cl-6-F-Ph, and X is O. 484 Q¹ is 2-Cl-4,6-di-F-Ph, and X is O. 485 Q¹ is 4-Cl-2,6-di-F-Ph, and X is O. 486 Q¹ is 2-Br-4-F-Ph, and X is O. 487 Q¹ is 2-Br-6-F-Ph, and X is O. 488 Q¹ is 2-Me-4-F-Ph, and X is O. 489 Q¹ is 2-I-4-F-Ph, and X is O. 490 Q¹ is 2-F-Ph, and X is O. 491 Q¹ is 2-Cl-Ph, and X is O. 492 Q¹ is 2-Br-Ph, and X is O. 493 Q¹ is 2-F-4-Cl-Ph, and X is O. 494 Q¹ is 2,4-di-Cl-Ph, and X is O. 495 Q¹ is 2,6-di-Cl-Ph, and X is O. 496 Q¹ is 2-F-4-MeO-Ph, and X is O. 497 Q¹ is 2-Cl-4-MeO-Ph, and X is O. 498 Q¹ is 2-Br-4-MeO-Ph, and X is O. 499 Q¹ is 2-F-4-CN-Ph, and X is O. 500 Q¹ is 2-Cl-4-CN-Ph, and X is O. 501 Q¹ is 2-Br-4-CN-Ph, and X is O. 502 Q¹ is 2,5-di-Cl-pyridin-3-yl, and X is O. 503 Q¹ is 2-Cl-thien-3-yl, and X is O. 504 Q¹ is 2,5-di-Cl-thien-3-yl, and X is O. 505 Q¹ is 2,6-di-F-Ph, and X is S. 506 Q¹ is 2,4-di-F-Ph, and X is S. 507 Q¹ is 2,4,6-tri-F-Ph, and X is S. 508 Q¹ is 2,6-di-F-4-OMe-Ph, and X is S. 509 Q¹ is 2,6-di-F-4-CN-Ph, and X is S. 510 Q¹ is 2-Cl-4-F-Ph, and X is S. 511 Q¹ is 2-Cl-6-F-Ph, and X is S. 512 Q¹ is 2-Cl-4,6-di-F-Ph, and X is S. 513 Q¹ is 4-Cl-2,6-di-F-Ph, and X is S. 514 Q¹ is 2-Br-4-F-Ph, and X is S. 515 Q¹ is 2-Br-6-F-Ph, and X is S. 516 Q¹ is 2-Me-4-F-Ph, and X is S. 517 Q¹ is 2-I-4-F-Ph, and X is S. 518 Q¹ is 2-F-Ph, and X is S. 519 Q¹ is 2-Cl-Ph, and X is S. 520 Q¹ is 2-Br-Ph, and X is S. 521 Q¹ is 2-F-4-Cl-Ph, and X is S. 522 Q¹ is 2,4-di-Cl-Ph, and X is S. 523 Q¹ is 2,6-di-Cl-Ph, and X is S. 524 Q¹ is 2-F-4-MeO-Ph, and X is S. 525 Q¹ is 2-Cl-4-MeO-Ph, and X is S. 526 Q¹ is 2-Br-4-MeO-Ph, and X is S. 527 Q¹ is 2-F-4-CN-Ph, and X is S. 528 Q¹ is 2-Cl-4-CN-Ph, and X is S. 529 Q¹ is 2-Br-4-CN-Ph, and X is S. 530 Q¹ is 2,5-di-Cl-3-pyridinyl, and X is S. 531 Q¹ is 2-Cl-3-thienyl, and X is S. 532 Q¹ is 2,5-di-Cl-3-thienyl, and X is S. 533 Q¹ is 2,6-di-F-Ph, and X is CHOH. 534 Q¹ is 2,4-di-F-Ph, and X is CHOH. 535 Q¹ is 2,4,6-tri-F-Ph, and X is CHOH. 536 Q¹ is 2,6-di-F-4-OMe-Ph, and X is CHOH. 537 Q¹ is 2,6-di-F-4-CN-Ph, and X is CHOH. 538 Q¹ is 2-Cl-4-F-Ph, and X is CHOH. 539 Q¹ is 2-Cl-6-F-Ph, and X is CHOH. 540 Q¹ is 2-Cl-4,6-di-F-Ph, and X is CHOH. 541 Q¹ is 4-Cl-2,6-di-F-Ph, and X is CHOH. 542 Q¹ is 2-Br-4-F-Ph, and X is CHOH. 543 Q¹ is 2-Br-6-F-Ph, and X is CHOH. 544 Q¹ is 2-Me-4-F-Ph, and X is CHOH. 545 Q¹ is 2-I-4-F-Ph, and X is CHOH. 546 Q¹ is 2-F-Ph, and X is CHOH. 547 Q¹ is 2-Cl-Ph, and X is CHOH. 548 Q¹ is 2-Br-Ph, and X is CHOH. 549 Q¹ is 2-F-4-Cl-Ph, and X is CHOH. 550 Q¹ is 2,4-di-Cl-Ph, and X is CHOH. 551 Q¹ is 2,6-di-Cl-Ph, and X is CHOH. 552 Q¹ is 2-F-4-MeO-Ph, and X is CHOH. 553 Q¹ is 2-Cl-4-MeO-Ph, and X is CHOH. 554 Q¹ is 2-Br-4-MeO-Ph, and X is CHOH. 555 Q¹ is 2-F-4-CN-Ph, and X is CHOH. 556 Q¹ is 2-Cl-4-CN-Ph, and X is CHOH. 557 Q¹ is 2-Br-4-CN-Ph, and X is CHOH. 558 Q¹ is 2,5-di-Cl-pyridin-3-yl, and X is CHOH. 559 Q¹ is 2,5-di-Cl-thien-3-yl, and X is CHOH. 560 Q¹ is 2,6-di-F-Ph, and X is C(O). 561 Q¹ is 2,4-di-F-Ph, and X is C(O). 562 Q¹ is 2,4,6-tri-F-Ph, and X is C(O). 563 Q¹ is 2,6-di-F-4-OM-Ph e, and X is C(O). 564 Q¹ is 2,6-di-F-4-CN-Ph, and X is C(O). 565 Q¹ is 2-Cl-4-F-Ph, and X is C(O). 566 Q¹ is 2-Cl-6-F-Ph, and X is C(O). 567 Q¹ is 2-Cl-4,6-di-F-Ph, and X is C(O). 568 Q¹ is 4-Cl-2,6-di-F-Ph, and X is C(O). 569 Q¹ is 2-Br-4-F-Ph, and X is C(O). 570 Q¹ is 2-Br-6-F-Ph, and X is C(O). 571 Q¹ is 2-Me-4-F-Ph, and X is C(O). 572 Q¹ is 2-I-4-F-Ph, and X is C(O). 573 Q¹ is 2-F-Ph, and X is C(O). 574 Q¹ is 2-Cl-Ph, and X is C(O). 575 Q¹ is 2-Br-Ph, and X is C(O). 576 Q¹ is 2-F-4-Cl-Ph, and X is C(O). 577 Q¹ is 2,4-di-Cl-Ph, and X is C(O). 578 Q¹ is 2,6-di-Cl-Ph, and X is C(O). 579 Q¹ is 2-F-4-MeO-Ph, and X is C(O). 580 Q¹ is 2-Cl-4-MeO-Ph, and X is C(O). 581 Q¹ is 2-Br-4-MeO-Ph, and X is C(O). 582 Q¹ is 2-F-4-CN-Ph, and X is C(O). 583 Q¹ is 2-Cl-4-CN-Ph, and X is C(O). 584 Q¹ is 2-Br-4-CN-Ph, and X is C(O). 585 Q¹ is 2,5-di-Cl-3-pyridinyl, and X is C(O). 586 Q¹ is 2-Cl-3-thienyl, and X is C(O). 587 Q¹ is 2,5-di-Cl-3-thienyl, and X is C(O).

TABLE 588

(R³)_(p) (R³)_(p) (R³)_(p) (R³)_(p) (R³)_(p) 2-F 3-F 4-F 2-Cl 3-Cl 4-Cl 2-Br 3-Br 4-Br 2,4-di-F 2,6-di-F 2,4,6-tri-F 2,4,5-tri-F 2,3,5-tri-F 2,3,6-tri-F 2-Cl-4-F 2-F-4-Cl 2,4-di-Cl 2,6-di-Cl 2,4,6-tri-Cl 2-Br-4-F 2-I-4-F 2-Me-4-F 2-F-4-MeO 2-Cl-4-MeO 2-Br-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-Cl-4-CN 2-Br-4-CN 2,6-di-F-4-CN 2-Cl-4,5-di-F 2-Cl-4,6-di-F 2-Br-4,5-di-F 2-Br-4,6-di-F 4-Cl-2,5-di-F 4-Cl-2,6-di-F 4-Br-2,5-di-F 4-Br-2,6-di-F 2,4-di-Cl-6-F 2,6-di-Cl-4-F 2,6-di-Cl-4-MeO 2-CF₃-4-F 4-Me 2,4-di-Me 2-F-4-Br 2-Cl-4-Br 2-Br-4-Cl 2-Br-4-F-6-Cl 2-Cl-4-Br-6-F Q¹is 2,6-di-F—Ph, and R² is Me.

The present disclosure also includes Tables 589 through 671, each of which is constructed the same as Table 588 above, except that the row heading in Table 588 (i.e. “Q¹ is 2,6-di-F-Ph, and R² is Me.”) is replaced with the respective row heading shown below. For Example, in Table 589 the row heading is “Q¹ is 2,6-di-F-Ph, and R² is Cl.”, and (R³)_(p) is as defined in Table 588 above. Thus, the first entry in Table 589 specifically discloses 5-chloro-4-(2,6-difluorophenyl)-N-(2-fluorophenyl)-1H-pyrazol-3-amine. Tables 589 through 671 are constructed similarly.

Table Row Heading 589 Q¹ is 2,6-di-F-Ph, and R² is Cl. 590 Q¹ is 2,6-di-F-Ph, and R² is Br. 591 Q¹ is 2,4-di-F-Ph, and R² is Me. 592 Q¹ is 2,4-di-F-Ph, and R² is Cl. 593 Q¹ is 2,4-di-F-Ph, and R² is Br. 594 Q¹ is 2,4,6-tri-F-Ph, and R² is Me. 595 Q¹ is 2,4,6-tri-F-Ph, and R² is Cl. 596 Q¹ is 2,4,6-tri-F-Ph, and R² is Br. 597 Q¹ is 2,6-di-F-4-OMe-Ph, and R² is Me. 598 Q¹ is 2,6-di-F-4-OMe-Ph, and R² is Cl. 599 Q¹ is 2,6-di-F-4-OMe-Ph, and R² is Br. 599A Q¹ is 2,6-di-F-4-OEt-Ph, and R² is Me. 599B Q¹ is 2,6-di-F-4-OEt-Ph, and R² is Cl. 599C Q¹ is 2,6-di-F-4-OEt-Ph, and R² is Br. 600 Q¹ is 2,6-di-F-4-CN-Ph, and R² is Me. 601 Q¹ is 2,6-di-F-4-CN-Ph, and R² is Cl. 602 Q¹ is 2,6-di-F-4-CN-Ph, and R² is Br. 603 Q¹ is 2-Cl-4-F-Ph, and R² is Me. 604 Q¹ is 2-Cl-4-F-Ph, and R² is Cl. 605 Q¹ is 2-Cl-4-F-Ph, and R² is Br. 606 Q¹ is 2-Cl-6-F-Ph, and R² is Me. 607 Q¹ is 2-Cl-6-F-Ph, and R² is Cl. 608 Q¹ is 2-Cl-6-F-Ph, and R² is Br. 609 Q¹ is 2-Cl-4,6-di-F-Ph, and R² is Me. 610 Q¹ is 2-Cl-4,6-di-F-Ph, and R² is Cl. 611 Q¹ is 2-Cl-4,6-di-F-Ph, and R² is Br. 612 Q¹ is 4-Cl-2,6-di-F-Ph, and R² is Me. 613 Q¹ is 4-Cl-2,6-di-F-Ph, and R² is Cl. 614 Q¹ is 4-Cl-2,6-di-F-Ph, and R² is Br. 615 Q¹ is 2-Br-4-F-Ph, and R² is Me. 616 Q¹ is 2-Br-4-F-Ph, and R² is Cl. 617 Q¹ is 2-Br-4-F-Ph, and R² is Br. 618 Q¹ is 2-Br-6-F-Ph, and R² is Me. 619 Q¹ is 2-Br-6-F-Ph, and R² is Cl. 620 Q¹ is 2-Br-6-F-Ph, and R² is Br. 621 Q¹ is 2-Me-4-F-Ph, and R² is Me. 622 Q¹ is 2-Me-4-F-Ph, and R² is Cl. 623 Q¹ is 2-Me-4-F-Ph, and R² is Br. 624 Q¹ is 2-I-4-F-Ph, and R² is Me. 625 Q¹ is 2-I-4-F-Ph, and R² is Cl. 626 Q¹ is 2-I-4-F-Ph, and R² is Br. 627 Q¹ is 2-F-Ph, and R² is Me. 628 Q¹ is 2-F-Ph, and R² is Cl. 629 Q¹ is 2-F-Ph, and R² is Br. 630 Q¹ is 2-Cl-Ph, and R² is Me. 631 Q¹ is 2-Cl-Ph, and R² is Cl. 632 Q¹ is 2-Cl-Ph, and R² is Br. 633 Q¹ is 2-Br-Ph, and R² is Me. 634 Q¹ is 2-Br-Ph, and R² is Cl. 635 Q¹ is 2-Br-Ph, and R² is Br. 636 Q¹ is 2-F-4-Cl-Ph, and R² is Me. 637 Q¹ is 2-F-4-Cl-Ph, and R² is Cl. 638 Q¹ is 2-F-4-Cl-Ph, and R² is Br. 639 Q¹ is 2,4-di-Cl-Ph, and R² is Me. 640 Q¹ is 2,4-di-Cl-Ph, and R² is Cl. 641 Q¹ is 2,4-di-Cl-Ph, and R² is Br. 642 Q¹ is 2,6-di-Cl-Ph, and R² is Me. 643 Q¹ is 2,6-di-Cl-Ph, and R² is Cl. 644 Q¹ is 2,6-di-Cl-Ph, and R² is Br. 645 Q¹ is 2-F-4-MeO-Ph, and R² is Me. 646 Q¹ is 2-F-4-MeO-Ph, and R² is Cl. 647 Q¹ is 2-F-4-MeO-Ph, and R² is Br. 647A Q¹ is 2-F-4-EtO-Ph, and R² is Me. 647B Q¹ is 2-F-4-EtO-Ph, and R² is Cl. 647C Q¹ is 2-F-4-EtO-Ph, and R² is Br. 648 Q¹ is 2-Cl-4-MeO-Ph, and R² is Me. 649 Q¹ is 2-Cl-4-MeO-Ph, and R² is Cl. 650 Q¹ is 2-Cl-4-MeO-Ph, and R² is Br. 650A Q¹ is 2-Cl-4-EtO-Ph, and R² is Me. 650B Q¹ is 2-Cl-4-EtO-Ph, and R² is Cl. 650C Q¹ is 2-Cl-4-EtO-Ph, and R² is Br. 651 Q¹ is 2-Br-4-MeO-Ph, and R² is Me. 652 Q¹ is 2-Br-4-MeO-Ph, and R² is Cl. 653 Q¹ is 2-Br-4-MeO-Ph, and R² is Br. 653A Q¹ is 2-Br-4-EtO-Ph, and R² is Me. 653B Q¹ is 2-Br-4-EtO-Ph, and R² is Cl. 653C Q¹ is 2-Br-4-EtO-Ph, and R² is Br. 654 Q¹ is 2-F-4-CN-Ph, and R² is Me. 655 Q¹ is 2-F-4-CN-Ph, and R² is Cl. 656 Q¹ is 2-F-4-CN-Ph, and R² is Br. 657 Q¹ is 2-Cl-4-CN-Ph, and R² is Me. 658 Q¹ is 2-Cl-4-CN-Ph, and R² is Cl. 659 Q¹ is 2-Cl-4-CN-Ph, and R² is Br. 660 Q¹ is 2-Br-4-CN-Ph, and R² is Me. 661 Q¹ is 2-Br-4-CN-Ph, and R² is Cl. 662 Q¹ is 2-Br-4-CN-Ph, and R² is Br. 663 Q¹ is 2,5-di-Cl-3-pyridinyl, and R² is Me. 664 Q¹ is 2,5-di-Cl-3-pyridinyl, and R² is Cl. 665 Q¹ is 2,5-di-Cl-3-pyridinyl, and R² is Br. 666 Q¹ is 2-Cl-3-thienyl, and R² is Me. 667 Q¹ is 2-Cl-3-thienyl, and R² is Cl. 668 Q¹ is 2-Cl-3-thienyl, and R² is Br. 669 Q¹ is 2,5-di-Cl-3-thienyl, and R² is Me. 670 Q¹ is 2,5-di-Cl-3-thienyl, and R² is Cl. 671 Q¹ is 2,5-di-Cl-3-thienyl, and R² is Br.

The compounds of Tables 588 through 671 illustrate compounds of Formula 2 wherein X is NH, which are useful intermediates to prepare compounds of Formula 1 using the method of Scheme 2.

TABLE 672

Q¹ Q¹ Q¹ Q¹ 2,6-di-F—Ph 2-Cl-4,6-di-F—Ph 2-Cl—Ph 2-Br-4-MeO—Ph 2,4-di-F—Ph 4-Cl-2,6-di-F—Ph 2-Br—Ph 2-F-4-CN—Ph 2,4,6-tri-F—Ph 2-Br-4-F—Ph 2-F-4-Cl—Ph 2-Cl-4-CN—Ph 2,6-di-F-4-OMe—Ph 2-Br-6-F—Ph 2,4-di-Cl—Ph 2-Br-4-CN—Ph 2,6-di-F-4-CN—Ph 2-Me-4-F—Ph 2,6-di-Cl—Ph 2,5-di-Cl-3-pyridinyl 2-Cl-4-F—Ph 2-I-4-F—Ph 2-F-4-MeO—Ph 2-Cl-3-thienyl 2-Cl-6-F—Ph 2-F—Ph 2-Cl-4-MeO—Ph 2,5-di-Cl-3-thienyl 2,6-di-F-4-EtO—Ph 2-F-4-EtO—Ph 2-Cl-4-EtO—Ph 2-Br-4-EtO—Ph G¹ is —OH.

The present disclosure also includes Tables 673 through 676, each of which is constructed the same as Table 672 above, except that the row heading in Table 672 (i.e. “G¹ is —OH.”) is replaced with the respective row heading shown below. For Example, in Table 673 the row heading is “G¹ is —SH.”, and Q¹ is as defined in Table 672 above. Thus, the first entry in Table 673 specifically discloses 4-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-thiol. Tables 674 through 676 are constructed similarly.

Table Row Heading 673 G¹ is —SH. 674 G¹ is Cl. 675 G¹ is Br. 675A G¹ is I. 676 G¹ is —NH₂.

The compounds of Tables 672 and 673 illustrate compounds of Formula 4 wherein X is O or S, R¹ and R^(1a) are each H, and R² is CH₃, which are useful intermediates to prepare compounds of Formula 1 using the method of Scheme 3. The compounds of Table 672 further illustrate compounds of Formula 4b wherein R¹ and R^(1a) are each H, and R² is CH₃, which are useful intermediates to prepare intermediate compounds of Formula 6a using the method of Scheme 6 and to prepare intermediate compounds of Formula 6b using the method of Scheme 7. Tables 674 and 675 illustrate compounds of Formula 6 wherein G is Cl or Br, and R^(1a) are each H, and R² is CH₃ which are useful intermediates to prepare compounds of Formula 1c using the method of Scheme 4. Table 676 illustrates compounds of Formula 4a wherein R¹ and R^(1a) are each H, and R² is CH₃, which are useful intermediates to prepare intermediate compounds of Formula 6 using the method of Scheme 5.

TABLE 677

(R³)_(p) (R³)_(p) (R³)_(p) (R³)_(p) (R³)_(p) 2-F 3-F 4-F 2-Cl 3-Cl 4-Cl 2-Br 3-Br 4-Br 2,4-di-F 2,6-di-F 2,4,6-tri-F 2,4,5-tri-F 2,3,5-tri-F 2,3,6-tri-F 2-Cl-4-F 2-F-4-Cl 2,4-di-Cl 2,6-di-Cl 2,4,6-tri-Cl 2-Br-4-F 2-I-4-F 2-Me-4-F 2-F-4-MeO 2-Cl-4-MeO 2-Br-4-MeO 2,6-di-F-4-MeO 2-F-4-CN 2-Cl-4-CN 2-Br-4-CN 2,6-di-F-4-CN 2-Cl-4,5-di-F 2-Cl-4,6-di-F 2-Br-4,5-di-F 2-Br-4,6-di-F 4-Cl-2,5-di-F 4-Cl-2,6-di-F 4-Br-2,5-di-F 4-Br-2,6-di-F 2,4-di-Cl-6-F 2,6-di-Cl-4-F 2,6-di-Cl-4-MeO 2-CF₃-4-F 4-Me 2,4-di-Me 2-F-4-Br 2-Cl-4-Br 2-Br-4-Cl 2-Br-4-F-6-Cl 2-Cl-4-Br-6-F Q¹ is 2,6-di-F—Ph, and R³² is Me.

The present disclosure also includes Tables 678 through 704, each of which is constructed the same as Table 677 above, except that the row heading in Table 677 (i.e. “Q¹ is 2,6-di-F-Ph.”) is replaced with the respective row heading shown below. For Example, in Table 2 the row heading is “Q¹ is 2,4-di-F-Ph.”, and (R³)_(p) is as defined in Table 677 above. Thus, the first entry in Table 678 specifically discloses 3-(2,6-difluorophenyl)-4-[(2,4-difluorophenyl)amino]-4-(methylthio)-3-buten-2-one. Tables 679 through 704 are constructed similarly.

Table Row Heading 678 Q¹ is 2,4-di-F-Ph, and R³² is Me. 679 Q¹ is 2,4,6-tri-F-Ph, and R³² is Me. 680 Q¹ is 2,6-di-F-4-OMe-Ph, and R³² is Me. 680A Q¹ is 2,6-di-F-4-OEt-Ph, and R³² is Me. 681 Q¹ is 2,6-di-F-4-CN-Ph, and R³² is Me. 682 Q¹ is 2-Cl-4-F-Ph, and R³² is Me. 683 Q¹ is 2-Cl-6-F-Ph, and R³² is Me. 684 Q¹ is 2-Cl-4,6-di-F-Ph, and R³² is Me. 685 Q¹ is 4-Cl-2,6-di-F-Ph, and R³² is Me. 686 Q¹ is 2-Br-4-F-Ph, and R³² is Me. 687 Q¹ is 2-Br-6-F-Ph, and R³² is Me. 688 Q¹ is 2-Me-4-F-Ph, and R³² is Me. 689 Q¹ is 2-I-4-F-Ph, and R³² is Me. 690 Q¹ is 2-F-Ph, and R³² is Me. 691 Q¹ is 2-Cl-Ph, and R³² is Me. 692 Q¹ is 2-Br-Ph, and R³² is Me. 693 Q¹ is 2-F-4-Cl-Ph, and R³² is Me. 694 Q¹ is 2,4-di-Cl-Ph, and R³² is Me. 695 Q¹ is 2,6-di-Cl-Ph, and R³² is Me. 696 Q¹ is 2-F-4-MeO-Ph, and R³² is Me. 696A Q¹ is 2-F-4-EtO-Ph, and R³² is Me. 697 Q¹ is 2-Cl-4-MeO-Ph, and R³² is Me. 697A Q¹ is 2-Cl-4-EtO-Ph, and R³² is Me. 698 Q¹ is 2-Br-4-MeO-Ph, and R³² is Me. 698A Q¹ is 2-Br-4-EtO-Ph, and R³² is Me. 699 Q¹ is 2-F-4-CN-Ph, and R³² is Me. 700 Q¹ is 2-Cl-4-CN-Ph, and R³² is Me. 701 Q¹ is 2-Br-4-CN-Ph, and R³² is Me. 702 Q¹ is 2,5-di-Cl-3-pyridinyl, and R³² is Me. 703 Q¹ is 2-Cl-3-thienyl, and R³² is Me. 704 Q¹ is 2,5-di-Cl-3-thienyl, and R³² is Me. 705 Q¹ is 2,6-di-F-Ph, and R³² is Et. 706 Q¹ is 2,4-di-F-Ph, and R³² is Et. 707 Q¹ is 2,4,6-tri-F-Ph, and R³² is Et. 708 Q¹ is 2,6-di-F-4-OMe-Ph, and R³² is Et. 708A Q¹ is 2,6-di-F-4-OEt-Ph, and R³² is Et. 709 Q¹ is 2,6-di-F-4-CN-Ph, and R³² is Et. 710 Q¹ is 2-Cl-4-F-Ph, and R³² is Et. 711 Q¹ is 2-Cl-6-F-Ph, and R³² is Et. 712 Q¹ is 2-Cl-4,6-di-F-Ph, and R³² is Et. 713 Q¹ is 4-Cl-2,6-di-F-Ph, and R³² is Et. 714 Q¹ is 2-Br-4-F-Ph, and R³² is Et. 715 Q¹ is 2-Br-6-F-Ph, and R³² is Et. 716 Q¹ is 2-Me-4-F-Ph, and R³² is Et. 717 Q¹ is 2-I-4-F-Ph, and R³² is Et. 718 Q¹ is 2-F-Ph, and R³² is Et. 719 Q¹ is 2-Cl-Ph, and R³² is Et. 720 Q¹ is 2-Br-Ph, and R³² is Et. 721 Q¹ is 2-F-4-Cl-Ph, and R³² is Et. 722 Q¹ is 2,4-di-Cl-Ph, and R³² is Et. 723 Q¹ is 2,6-di-Cl-Ph, and R³² is Et. 724 Q¹ is 2-F-4-MeO-Ph, and R³² is Et. 724A Q¹ is 2-F-4-EtO-Ph, and R³² is Et. 725 Q¹ is 2-Cl-4-MeO-Ph, and R³² is Et. 725A Q¹ is 2-Cl-4-EtO-Ph, and R³² is Et. 726 Q¹ is 2-Br-4-MeO-Ph, and R³² is Et. 726A Q¹ is 2-Br-4-EtO-Ph, and R³² is Et. 727 Q¹ is 2-F-4-CN-Ph, and R³² is Et. 728 Q¹ is 2-Cl-4-CN-Ph, and R³² is Et. 729 Q¹ is 2-Br-4-CN-Ph, and R³² is Et. 730 Q¹ is 2,5-di-Cl-3-pyridinyl, and R³² is Et. 731 Q¹ is 2-Cl-3-thienyl, and R³² is Et. 732 Q¹ is 2,5-di-Cl-3-thienyl, and R³² is Et. 733 Q¹ is 2,6-di-F-Ph, and R³² is n-Pr. 734 Q¹ is 2,4-di-F-Ph, and R³² is n-Pr. 735 Q¹ is 2,4,6-tri-F-Ph, and R³² is n-Pr. 736 Q¹ is 2,6-di-F-4-OMe-Ph, and R³² is n-Pr. 736A Q¹ is 2,6-di-F-4-OEt-Ph, and R³² is n-Pr. 737 Q¹ is 2,6-di-F-4-CN-Ph, and R³² is n-Pr. 738 Q¹ is 2-Cl-4-F-Ph, and R³² is n-Pr. 739 Q¹ is 2-Cl-6-F-Ph, and R³² is n-Pr. 740 Q¹ is 2-Cl-4,6-di-F-Ph, and R³² is n-Pr. 741 Q¹ is 4-Cl-2,6-di-F-Ph, and R³² is n-Pr. 742 Q¹ is 2-Br-4-F-Ph, and R³² is n-Pr. 743 Q¹ is 2-Br-6-F-Ph, and R³² is n-Pr. 744 Q¹ is 2-Me-4-F-Ph, and R³² is n-Pr. 745 Q¹ is 2-I-4-F-Ph, and R³² is n-Pr. 746 Q¹ is 2-F-Ph, and R³² is n-Pr. 747 Q¹ is 2-Cl-Ph, and R³² is n-Pr. 748 Q¹ is 2-Br-Ph, and R³² is n-Pr. 749 Q¹ is 2-F-4-Cl-Ph, and R³² is n-Pr. 750 Q¹ is 2,4-di-Cl-Ph, and R³² is n-Pr. 751 Q¹ is 2,6-di-Cl-Ph, and R³² is n-Pr. 752 Q¹ is 2-F-4-MeO-Ph, and R³² is n-Pr. 752A Q¹ is 2-F-4-EtO-Ph, and R³² is n-Pr. 753 Q¹ is 2-Cl-4-MeO-Ph, and R³² is n-Pr. 753A Q¹ is 2-Cl-4-EtO-Ph, and R³² is n-Pr. 754 Q¹ is 2-Br-4-MeO-Ph, and R³² is n-Pr. 754A Q¹ is 2-Br-4-EtO-Ph, and R³² is n-Pr. 755 Q¹ is 2-F-4-CN-Ph, and R³² is n-Pr. 756 Q¹ is 2-Cl-4-CN-Ph, and R³² is n-Pr. 757 Q¹ is 2-Br-4-CN-Ph, and R³² is n-Pr. 758 Q¹ is 2,5-di-Cl-3-pyridinyl, and R³² is n-Pr. 759 Q¹ is 2-Cl-3-thienyl, and R³² is n-Pr. 760 Q¹ is 2,5-di-Cl-3-thienyl, and R³² is n-Pr.

The compounds of Tables 677 through 760 illustrate compounds of Formula 17 wherein R² is CH₃, which are useful intermediates to prepare compounds of Formula 1c using the method of Scheme 16.

TABLE 761

Q¹ Q¹ Q¹ Q¹ 2,6-di-F—Ph 2-Cl-4,6-di-F—Ph 2-Cl—Ph 2-Br-4-MeO—Ph 2,4-di-F—Ph 4-Cl-2,6-di-F—Ph 2-Br—Ph 2-F-4-CN—Ph 2,4,6-tri-F—Ph 2-Br-4-F—Ph 2-F-4-Cl—Ph 2-Cl-4-CN—Ph 2,6-di-F-4-OMe—Ph 2-Br-6-F—Ph 2,4-di-Cl—Ph 2-Br-4-CN—Ph 2,6-di-F-4-CN—Ph 2-Me-4-F—Ph 2,6-di-Cl—Ph 2,5-di-Cl-3-pyridinyl 2-Cl-4-F—Ph 2-I-4-F—Ph 2-F-4-MeO—Ph 2-Cl-3-thienyl 2-Cl-6-F—Ph 2-F—Ph 2-Cl-4-MeO—Ph 2,5-di-Cl-3-thienyl 2,6-di-F-4-EtO—Ph 2-F-4-EtO—Ph 2-Cl-4-EtO—Ph 2-Br-4-EtO—Ph Each R³³ is Me.

The present disclosure also includes Tables 762 through 764, each of which is constructed the same as Table 761 above, except that the row heading in Table 761 (i.e. “Each R³³ is Me.”) is replaced with the respective row heading shown below. For Example, in Table 762 the row heading is “Each R³³ is Et.”, and Q¹ is as defined in Table 761 above. Thus, the first entry in Table 762 specifically discloses 3-(2,6-difluorophenyl)-4,4-bis(ethylthio)-3-buten-2-one. Tables 763 and 764 are constructed similarly.

Table Row Heading 762 Each R³³ is Et. 763 Each R³³ is n-Pr. 764 The two R³³ are taken together as —CH₂—.

The compounds of Tables 761 through 763 illustrate compounds of Formula 18 wherein R² is CH₃, which are useful intermediates to prepare intermediate compounds of Formula 17 using the method of Scheme 17. The compounds of Table 764 illustrate compounds of Formula 18 wherein R² is CH₃, which are useful intermediates to prepare intermediate compounds of Formula 4c using the method described below Scheme 17.

TABLE 765

Q¹ Q¹ Q¹ Q¹ 2,6-di-F—Ph 2-Cl-4,6-di-F—Ph 2-Cl—Ph 2-Br-4-MeO—Ph 2,4-di-F—Ph 4-Cl-2,6-di-F—Ph 2-Br—Ph 2-F-4-CN—Ph 2,4,6-tri-F—Ph 2-Br-4-F—Ph 2-F-4-Cl—Ph 2-Cl-4-CN—Ph 2,6-di-F-4-OMe—Ph 2-Br-6-F—Ph 2,4-di-Cl—Ph 2-Br-4-CN—Ph 2,6-di-F-4-CN—Ph 2-Me-4-F—Ph 2,6-di-Cl—Ph 2,5-di-Cl-3-pyridinyl 2-Cl-4-F—Ph 2-I-4-F—Ph 2-F-4-MeO—Ph 2-Cl-3-thienyl 2-Cl-6-F—Ph 2-F—Ph 2-Cl-4-MeO—Ph 2,5-di-Cl-3-thienyl 2,6-di-F-4-EtO—Ph 2-F-4-EtO—Ph 2-Cl-4-EtO—Ph 2-Br-4-EtO—Ph B¹ is Me.

The present disclosure also includes Tables 766 through 769, each of which is constructed the same as Table 765 above, except that the row heading in Table 765 (i.e. “B¹ is Me.”) is replaced with the respective row heading shown below. For Example, in Table 766 the row heading is “B¹ is Et.”, and Q¹ is as defined in Table 765 above. Thus, the first entry in Table 766 specifically discloses ethyl α-acetyl-2,6-difluorobenzeneacetate. Tables 767 through 769 are constructed similarly

Table Row Heading 766 B¹ is Et. 767 B¹ is is n-Pr. 768 B¹ is Ph. 769 B¹ is CH₂Ph.

The compounds of Tables 765 through 769 illustrate compounds of Formula 16 wherein R² is CH₃, which are useful intermediates to prepare intermediate compounds of Formula 4b using the method of Scheme 14.

Formulation/Utility

A compound of this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.

Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.

The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible (“wettable”) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or “overcoated”). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.

Sprayable formulations are typically extended in a suitable medium before spraying. Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other desirable vegetation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.

The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.

Weight Percent Active Ingredient Diluent Surfactant Water-Dispersible and Water- 0.001-90 0-99.999  0-15 soluble Granules, Tablets and Powders Oil Dispersions, Suspensions,    1-50 40-99     0-50 Emulsions, Solutions (including Emulsifiable Concentrates) Dusts    1-25 70-99    0-5 Granules and Pellets 0.001-95 5-99.999  0-15 High Strength Compositions   90-99 0-10    0-2

Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, N.J.

Liquid diluents include, for example, water, N,N-dimethylalkanamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C₆-C₂₂), such as plant seed and fruit oils (e.g, oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.

The solid and liquid compositions of the present invention often include one or more surfactants. When added to a liquid, surfactants (also known as “surface-active agents”) generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in a surfactant molecule, surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.

Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as N,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as N-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.

Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also function as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.

The compound of Formula 1 and any other active ingredients are typically incorporated into the present compositions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. Pat. No. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 m range. Dusts and powders can be prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, “Agglomeration”, Chemical Engineering, Dec. 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. Pat. No. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. Pat. Nos. 4,144,050, 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. Pat. Nos. 5,180,587, 5,232,701 and 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. Pat. No. 3,299,566.

For further information regarding the art of formulation, see T. S. Woods, “The Formulator's Toolbox—Product Forms for Modern Agriculture” in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. Pat. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, U K, 2000.

In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Table A. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.

Example A

High Strength Concentrate Compound 18 98.5% silica aerogel  0.5% synthetic amorphous fine silica  1.0%

Example B

Wettable Powder Compound 22 65.0% dodecylphenol polyethylene glycol ether  2.0% sodium ligninsulfonate  4.0% sodium silicoaluminate  6.0% montmorillonite (calcined) 23.0%

Example C

Granule Compound 23 10.0% attapulgite granules (low volatile matter, 90.0% 0.71/0.30 mm; U.S.S. No. 25-50 sieves)

Example D

Extruded Pellet Compound 24 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate  5.0% sodium alkylnaphthalenesulfonate  1.0% calcium/magnesium bentonite 59.0%

Example E

Emulsifiable Concentrate Compound 36 10.0% polyoxyethylene sorbitol hexoleate 20.0% C₆—C₁₀ fatty acid methyl ester 70.0%

Example F

Microemulsion Compound 41  5.0% polyvinylpyrrolidone-vinyl acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%

Example G

Seed Treatment Compound 45 20.00% polyvinylpyrrolidone-vinyl acetate copolymer  5.00% montan acid wax  5.00% calcium ligninsulfonate  1.00% polyoxyethylene/polyoxypropylene block copolymers  1.00% stearyl alcohol (POE 20)  2.00% polyorganosilane  0.20% colorant red dye  0.05% water 65.75%

Formulations such as those in the Formulation Table are typically diluted with water to form aqueous compositions before application. Aqueous compositions for direct applications to the plant or portion thereof (e.g., spray tank compositions) typically at least about 1 ppm or more (e.g., from 1 ppm to 100 ppm) of the compound(s) of this invention.

The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe polygoni), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rutstroemia floccosum (also known as Sclerontina homoeocarpa); Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium diseases such as Fusarium roseum, Fusarium gramninearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species.

Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The compounds can also be applied through irrigation water to treat plants.

Accordingly, this aspect of the present invention can also be described as a method for protecting a plant or plant seed from diseases caused by fungal pathogens comprising applying a fungicidally effective amount of a compound of Formula 1, an N-oxide, or salt thereof to the plant (or portion thereof) or plant seed (directly or through the environment (e.g., growing medium) of the plant or plant seed).

Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 10 g per kilogram of seed.

Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Thus the present invention also pertains to a composition comprising a fungicidally effective amount of a compound of Formula 1 and a biologically effective amount of at least one additional biologically active compound or agent and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.

As mentioned in the Summary of the Invention, one aspect of the present invention is a fungicidal composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof (i.e. component a), and at least one other fungicide (i.e. component b).

Of note is a composition which, in addition to the Formula 1 compound of component (a), includes as component (b) at least one fungicidal compound selected from the group consisting of the classes (b1) methyl benzimidazole carbamate (MBC) fungicides; (b2) dicarboximide fungicides; (b3) demethylation inhibitor (DMI) fungicides; (b4) phenylamide fungicides; (b5) amine/morpholine fungicides; (b6) phospholipid biosynthesis inhibitor fungicides; (b7) carboxamide fungicides; (b8) hydroxy(2-amino-)pyrimidine fungicides; (b9) anilinopyrimidine fungicides; (b10) N-phenyl carbamate fungicides; (b11) quinone outside inhibitor (QoI) fungicides; (b12) phenylpyrrole fungicides; (b13) quinoline fungicides; (b14) lipid peroxidation inhibitor fungicides; (b15) melanin biosynthesis inhibitors-reductase (MBI-R) fungicides; (b16) melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides; (b17) hydroxyanilide fungicides; (b18) squalene-epoxidase inhibitor fungicides; (b19) polyoxin fungicides; (b20) phenylurea fungicides; (b21) quinone inside inhibitor (QiI) fungicides; (b22) benzamide fungicides; (b23) enopyranuronic acid antibiotic fungicides; (b24) hexopyranosyl antibiotic fungicides; (b25) glucopyranosyl antibiotic: protein synthesis fungicides; (b26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides; (b27) cyanoacetamideoxime fungicides; (b28) carbamate fungicides; (b29) oxidative phosphorylation uncoupling fungicides; (b30) organo tin fungicides; (b31) carboxylic acid fungicides; (b32) heteroaromatic fungicides; (b33) phosphonate fungicides; (b34) phthalamic acid fungicides; (b35) benzotriazine fungicides; (b36) benzene-sulfonamide fungicides; (b37) pyridazinone fungicides; (b38) thiophene-carboxamide fungicides; (b39) pyrimidinamide fungicides; (b40) carboxylic acid amide (CAA) fungicides; (b41) tetracycline antibiotic fungicides; (b42) thiocarbamate fungicides; (b43) benzamide fungicides; (b44) host plant defense induction fungicides; (b45) multi-site contact activity fungicides; (b46) fungicides other than classes (b1) through (b45); and salts of compounds of classes (b1) through (b46).

Further descriptions of these classes of fungicidal compounds are provided below.

(b1) “Methyl benzimidazole carbamate (MBC) fungicides” (FRAC (Fungicide Resistance Action Committee) code 1) inhibit mitosis by binding to β-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. The benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include thiophanate and thiophanate-methyl.

(b2) “Dicarboximide fungicides” (FRAC code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.

(b3) “Demethylation inhibitor (DMI) fungicides” (FRAC code 3) inhibit C14-demethylase which plays a role in sterol production. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides result in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz, pefurazoate and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides—Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.

(b4) “Phenylamide fungicides” (FRAC code 4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide. Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides. The acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M (also known as mefenoxam). The oxazolidinones include oxadixyl. The butyrolactones include ofurace.

(b5) “Amine/morpholine fungicides” (FRAC code 5) inhibit two target sites within the sterol biosynthetic pathway, Δ⁸→Δ⁷ isomerase and Δ¹⁴ reductase. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides. The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.

(b6) “Phospholipid biosynthesis inhibitor fungicides” (FRAC code 6) inhibit growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phosphorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.

(b7) “Carboxamide fungicides” (FRAC code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction. Carboxamide fungicides include benzamide, furan carboxamide, oxathiin carboxamide, thiazole carboxamide, pyrazole carboxamide and pyridine carboxamide. The benzamides include benodanil, flutolanil and mepronil. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole carboxamides include bixafen, furametpyr, isopyrazam, fluxapyroxad, sedaxane (N-[2-(1S,2R)-[1,1′-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) and penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149)). The pyridine carboxamides include boscalid.

(b8) “Hydroxy(2-amino-)pyrimidine fungicides” (FRAC code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.

(b9) “Anilinopyrimidine fungicides” (FRAC code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.

(b10) “N-Phenyl carbamate fungicides” (FRAC code 10) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.

(b11) “Quinone outside inhibitor (QoI) fungicides” (FRAC code 11) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the “quinone outside” (Q_(o)) site of the cytochrome bc₁ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides (also known as strobilurin fungicides) include methoxyacrylate, methoxycarbamate, oximinoacetate, oximinoacetamide, oxazolidinedione, dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. The methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin. The methoxycarbamates include pyraclostrobin and pyrametostrobin. The oximinoacetates include kresoxim-methyl, pyraoxystrobin and trifloxystrobin. The oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin, α-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl)phenyl]ethoxy]imino]-methyl]benzeneacetamide and 2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]-amino]oxy]methyl]-α-(methoxyimino)-N-methylbenzeneacetamide. The oxazolidinediones include famoxadone. The dihydrodioxazines include fluoxastrobin. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb.

(b12) “Phenylpyrrole fungicides” (FRAC code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi. Fenpiclonil and fludioxonil are examples of this fungicide class.

(b13) “Quinoline fungicides” (FRAC code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.

(b14) “Lipid peroxidation inhibitor fungicides” (FRAC code 14) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic carbon and 1,2,4-thiadiazole fungicides. The aromatic carbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos-methyl. The 1,2,4-thiadiazole fungicides include etridiazole.

(b15) “Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides” (FRAC code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole.

(b16) “Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides” (FRAC code 16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin in required for host plant infection by some fungi. Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil.

(b17) “Hydroxyanilide fungicides (FRAC code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid.

(b18) “Squalene-epoxidase inhibitor fungicides” (FRAC code 18) inhibit squalene-epoxidase in ergosterol biosynthesis pathway. Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Squalene-epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifine and terbinafine.

(b19) “Polyoxin fungicides” (FRAC code 19) inhibit chitin synthase. Examples include polyoxin.

(b20) “Phenylurea fungicides” (FRAC code 20) are proposed to affect cell division. Examples include pencycuron.

(b21) “Quinone inside inhibitor (QiI) fungicides” (FRAC code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the “quinone inside” (Q_(i)) site of the cytochrome bc₁ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom.

(b22) “Benzamide fungicides” (FRAC code 22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.

(b23) “Enopyranuronic acid antibiotic fungicides” (FRAC code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.

(b24) “Hexopyranosyl antibiotic fungicides” (FRAC code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin.

(b25) “Glucopyranosyl antibiotic: protein synthesis fungicides” (FRAC code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.

(b26) “Glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides” (FRAC code 26) inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin.

(b27) “Cyanoacetamideoxime fungicides (FRAC code 27) include cymoxanil.

(b28) “Carbamate fungicides” (FRAC code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, propamacarb-hydrochloride, iodocarb, and prothiocarb are examples of this fungicide class.

(b29) “Oxidative phosphorylation uncoupling fungicides” (FRAC code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.

(b30) “Organo tin fungicides” (FRAC code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway. Examples include fentin acetate, fentin chloride and fentin hydroxide.

(b31) “Carboxylic acid fungicides” (FRAC code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid.

(b32) “Heteroaromatic fungicides” (FRAC code 32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone fungicides. The isoxazoles include hymexazole and the isothiazolones include octhilinone.

(b33) “Phosphonate fungicides” (FRAC code 33) include phosphorous acid and its various salts, including fosetyl-aluminum.

(b34) “Phthalamic acid fungicides” (FRAC code 34) include teclofthalam.

(b35) “Benzotriazine fungicides” (FRAC code 35) include triazoxide.

(b36) “Benzene-sulfonamide fungicides” (FRAC code 36) include flusulfamide.

(b37) “Pyridazinone fungicides” (Fungicide Resistance Action Committee (FRAC) code 37) include diclomezine.

(b38) “Thiophene-carboxamide fungicides” (FRAC code 38) are proposed to affect ATP production. Examples include silthiofam.

(b39) “Pyrimidinamide fungicides” (FRAC code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.

(b40) “Carboxylic acid amide (CAA) fungicides” (FRAC code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides. The cinnamic acid amides include dimethomorph and flumorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valifenalate (valiphenal). The mandelic acid amides include mandipropamid, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)-amino]butanamide and N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]-ethyl]-3-methyl-2-[(ethyl sulfonyl)amino]butanamide.

(b41) “Tetracycline antibiotic fungicides” (FRAC code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline.

(b42) “Thiocarbamate fungicides (b42)” (FRAC code 42) include methasulfocarb.

(b43) “Benzamide fungicides” (FRAC code 43) inhibit growth of fungi by delocalization of spectrin-like proteins. Examples include acylpicolide fungicides such as fluopicolide and fluopyram.

(b44) “Host plant defense induction fungicides” (FRAC code P) induce host plant defense mechanisms. Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides. The benzo-thiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole-carboxamides include tiadinil and isotianil.

(b45) “Multi-site contact fungicides” inhibit fungal growth through multiple sites of action and have contact/preventive activity. This class of fungicides includes: (b45.1) “copper fungicides” (FRAC code M1)”, (b45.2) “sulfur fungicides” (FRAC code M2), (b45.3) “dithiocarbamate fungicides” (FRAC code M3), (b45.4) “phthalimide fungicides” (FRAC code M4), (b45.5) “chloronitrile fungicides” (FRAC code M5), (b45.6) “sulfamide fungicides” (FRAC code M6), (b45.7) “guanidine fungicides” (FRAC code M7), (b45.8) “triazine fungicides” (FRAC code M8) and (b45.9) “quinone fungicides” (FRAC code M9). “Copper fungicides” are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). “Sulfur fungicides” are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur. “Dithiocarbamate fungicides” contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram. “Phthalimide fungicides” contain a phthalimide molecular moiety; examples include folpet, captan and captafol. “Chloronitrile fungicides” contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. “Sulfamide fungicides” include dichlofluanid and tolyfluanid. “Guanidine fungicides” include dodine, guazatine and imoctadine, including iminoctadine albesilate and iminoctadine triacetate. “Triazine fungicides” include anilazine. “Quinone fungicides” include dithianon.

(b46) “Fungicides other than fungicides of classes (b1) through (b45)” include certain fungicides whose mode of action may be unknown. These include: (b46.1) “thiazole carboxamide fungicides” (FRAC code US), (b46.2) “phenyl-acetamide fungicides” (FRAC code U6), (b46.3) “quinazolinone fungicides” (FRAC code U7) and (b46.4) “benzophenone fungicides” (FRAC code U8). The thiazole carboxamides include ethaboxam. The phenyl-acetamides include cyflufenamid and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]-methylene]benzeneacetamide. The quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one. The benzophenones include metrafenone and pyriofenone. The (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), fenpyrazamine, pyrrolnitrin, quinomethionate, tebufloquin, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methyl sulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]-butanamide, 2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, 4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl)[1,2,4]triazolo[1,5-a]pyrimidine, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, N-[[(cyclopropylmethoxy)-amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, N-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide and 1-[(2-propenylthio)carbonyl]-2-(1-methylethyl)-4-(2-methylphenyl)-5-amino-1H-pyrazol-3-one.

Therefore of note is a mixture (i.e. composition) comprising as component (a) a compound of Formula 1 (or an N-oxide or salt thereof) and as component (b) at least one fungicidal compound selected from the group consisting of the aforedescribed classes (b1) through (b46). Also of note are embodiments wherein component (b) comprises at least one fungicide from each of two different groups selected from (b1) through (b46). Also of note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of particular note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (b1) through (b46). Also of particular note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents.

Examples of other biologically active compounds or agents with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet (S-1955), amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole (DPX-E2Y45), chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyantraniliprole (3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)-carbonyl]phenyl]-1H-pyrazole-5-carboxamide), cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim (UR-50701), flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron (XDE-007), noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, prothiocarb, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen (BSN 2060), spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron; nematocides such as aldicarb, imicyafos, oxamyl and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyenopyrafen, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents including entomopathogenic bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as CpGV.

General references for agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U. K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U. K., 2001.

For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 (or an N-oxide or salt thereof) is typically between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (for example ratios between about 1:30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.

In certain instances, combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.

Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). The effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins.

Of note is a combination of a compound of Formula 1 (or an N-oxide or salt thereof) with at least one other fungicidal active ingredient. Of particular note is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1. In certain instances, a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action.

Of particular note are compositions which in addition to a compound of Formula 1 include at least one compound selected from the group consisting of (1) alkylenebis(dithiocarbamate) fungicides; (2) cymoxanil; (3) phenylamide fungicides; (4) pyrimidinone fungicides; (5) chlorothalonil; (6) carboxamides acting at complex II of the fungal mitochondrial respiratory electron transfer site; (7) quinoxyfen; (8) metrafenone or pyriofenone; (9) cyflufenamid; (10) cyprodinil; (11) copper compounds; (12) phthalimide fungicides; (13) fosetyl-aluminum; (14) benzimidazole fungicides; (15) cyazofamid; (16) fluazinam; (17) iprovalicarb; (18) propamocarb; (19) validomycin; (20) dichlorophenyl dicarboximide fungicides; (21) zoxamide; (22) fluopicolide; (23) mandipropamid; (24) carboxylic acid amides acting on phospholipid biosynthesis and cell wall deposition; (25) dimethomorph; (26) non-DMI sterol biosynthesis inhibitors; (27) inhibitors of demethylase in sterol biosynthesis; (28) bc₁ complex fungicides; and salts of compounds of (1) through (28).

Further descriptions of classes of fungicidal compounds are provided below.

Pyrimidinone fungicides (group (4)) include compounds of Formula A1

wherein M forms a fused phenyl, thiophene or pyridine ring; R^(a14) is C₁-C₆ alkyl; R^(a15) is C₁-C₆ alkyl or C₁-C₆ alkoxy; R^(a16) is halogen; and R^(a17) is hydrogen or halogen.

Pyrimidinone fungicides are described in PCT Patent Application Publication WO 94/26722 and U.S. Pat. Nos. 6,066,638, 6,245,770, 6,262,058 and 6,277,858. Of note are pyrimidinone fungicides selected from the group: 6-bromo-3-propyl-2-propyloxy-4(3H)-quinazolinone, 6,8-diiodo-3-propyl-2-propyloxy-4(3H)-quinazolinone, 6-iodo-3-propyl-2-propyloxy-4(3H)-quinazolinone (proquinazid), 6-chloro-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3-propylthieno[2,3-d]pyrimidin-4(3H)-one, 7-bromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one, 6-bromo-2-propoxy-3-propylpyrido[2,3-d]pyrimidin-4(3H)-one, 6,7-dibromo-2-propoxy-3-propylthieno[3,2-d]pyrimidin-4(3H)-one, and 3-(cyclopropylmethyl)-6-iodo-2-(propylthio)pyrido-[2,3-d]pyrimidin-4(3H)-one.

Sterol biosynthesis inhibitors (group (27)) control fungi by inhibiting enzymes in the sterol biosynthesis pathway. Demethylase-inhibiting fungicides have a common site of action within the fungal sterol biosynthesis pathway, involving inhibition of demethylation at position 14 of lanosterol or 24-methylene dihydrolanosterol, which are precursors to sterols in fungi. Compounds acting at this site are often referred to as demethylase inhibitors, DMI fungicides, or DMIs. The demethylase enzyme is sometimes referred to by other names in the biochemical literature, including cytochrome P-450 (14DM). The demethylase enzyme is described in, for example, J. Biol. Chem. 1992, 267, 13175-79 and references cited therein. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, econazole, imazalil, isoconazole, miconazole, oxpoconazole, prochloraz and triflumizole. The pyrimidines include fenarimol, nuarimol and triarimol. The piperazines include triforine. The pyridines include buthiobate and pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides—Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.

bc₁ Complex Fungicides (group 28) have a fungicidal mode of action which inhibits the bc₁ complex in the mitochondrial respiration chain. The bc₁ complex is sometimes referred to by other names in the biochemical literature, including complex III of the electron transfer chain, and ubihydroquinone:cytochrome c oxidoreductase. This complex is uniquely identified by Enzyme Commission number EC1.10.2.2. The bc₁ complex is described in, for example, J. Biol. Chem. 1989, 264, 14543-48; Methods Enzymol. 1986, 126, 253-71; and references cited therein. Strobilurin fungicides such as azoxystrobin, dimoxystrobin, enestroburin (SYP-Z071), fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin and trifloxystrobin are known to have this mode of action (H. Sauter et al., Angew. Chem. Int. Ed. 1999, 38, 1328-1349). Other fungicidal compounds that inhibit the bc₁ complex in the mitochondrial respiration chain include famoxadone and fenamidone.

Alkylenebis(dithiocarbamate)s (group (1)) include compounds such as mancozeb, maneb, propineb and zineb. Phenylamides (group (3)) include compounds such as metalaxyl, benalaxyl, furalaxyl and oxadixyl. Carboxamides (group (6)) include compounds such as boscalid, carboxin, fenfuram, flutolanil, fluxapyroxad, furametpyr, mepronil, oxycarboxin, thifluzamide, penthiopyrad and penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide (PCT Patent Publication WO 2003/010149)), and are known to inhibit mitochondrial function by disrupting complex II (succinate dehydrogenase) in the respiratory electron transport chain. Copper compounds (group (11)) include compounds such as copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). Phthalimides (group (12)) include compounds such as folpet and captan. Benzimidazole fungicides (group (14)) include benomyl and carbendazim. Dichlorophenyl dicarboximide fungicides (group (20)) include chlozolinate, dichlozoline, iprodione, isovaledione, myclozolin, procymidone and vinclozolin.

Non-DMI sterol biosynthesis inhibitors (group (26)) include morpholine and piperidine fungicides. The morpholines and piperidines are sterol biosynthesis inhibitors that have been shown to inhibit steps in the sterol biosynthesis pathway at a point later than the inhibitions achieved by the DMI sterol biosynthesis (group (27)). The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin.

Examples of component (b) fungicides include acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl, benalaxyl-M, benodanil, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolinate, clotrimazole, copper salts such as Bordeaux mixture (tribasic copper sulfate), copper hydroxide and copper oxychloride, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, dithianon, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin chloride, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluopicolide (also known as picobenzamid), fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil (2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazolidinylidene]acetonitrile), flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazol, guazatine, imazalil, imibenconazole, iminoctadine, iodocarb, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, maneb, mepronil, meptyldinocap, metalaxyl, metalaxyl-M, metconazole, methasulfocarb, metiram, metominostrobin, mepanipyrim, metrafenone, myclobutanil, naftifine, neo-asozin (ferric methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen, penthiopyrad, pefurazoate, phosphorous acid and salts, phthalide, picoxystrobin, piperalin, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propamocarb-hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyrrolnitrin, quinomethionate, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, tecloftalam, tecnazene, terbinafine, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, triflumizole, tricyclazole, trifloxystrobin, triforine, trimorphamide, triticonazole, uniconazole, validamycin, valifenalate (valiphenal), vinclozolin, zineb, ziram, zoxamide, N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, 5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin-1-yl)[1,2,4]triazolo[1,5-a]pyrimidine (BAS600), penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide), N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methyl sulfonyl)amino]butanamide, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide, 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]-pyridine, 4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, α-(methoxyimino)-N-methyl-2-[[[1-[3-(trifluoro-methyl)phenyl]ethoxy]imino]methyl]benzeneacetamide, N-[4-[4-chloro-3-(trifluoro-methyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimidamide, N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methylbenzenesulfonamide, 2-[[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1-ylidene]amino]oxy]methyl]-α-(methoxyimino)-N-methylbenzeneacetamide, 1-[(2-propenylthio)carbonyl]-2-(1-methylethyl)-4-(2-methylphenyl)-5-amino-1H-pyrazol-3-one, ethyl-6-octyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ylamine, pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-thiazolyl]carbamate and pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenylmethylene]amino]oxy]methyl]-2-pyridinyl]carbamate

Of note are combinations of compounds of Formula 1 (or an N-oxide or salt thereof) (i.e. Component (a) in compositions) with azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, pyrametostrobin, pyraoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, carbendazim, chlorothalonil, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, bromuconazole, cyproconazole, difenoconazole, epoxiconazole, fenbuconazole, flusilazole, fluxapyroxad, hexaconazole, ipconazole, metconazole, penconazole, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone, prochloraz, penthiopyrad and boscalid (nicobifen) (i.e. as Component (b) in compositions).

Preferred for better control of plant diseases caused by fungal plant pathogens (e.g., lower use rate or broader spectrum of plant pathogens controlled) or resistance management are mixtures of a compound of this invention with a fungicide selected from the group: azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, picoxystrobin, pyrametostrobin, pyraoxystrobin, dimoxystrobin, metominostrobin/fenominostrobin, quinoxyfen, metrafenone, cyflufenamid, fenpropidine, fenpropimorph, cyproconazole, epoxiconazole, flusilazole, metconazole, propiconazole, proquinazid, prothioconazole, pyriofenone, tebuconazole, triticonazole, famoxadone and penthiopyrad.

Tables A1 through A54 list specific combinations of a Component (b) compound with Component (a) (compound numbers refer to compounds in Index Table A) illustrative of the mixtures, compositions and methods of the present invention. In Table A1, each line below the column headings “Component (a)” and “Component (b)” specifically discloses a combination (i.e. mixture) of Component (a), which is Compound 22, with a Component (b) fungicide. The entries under the heading “Illustrative Ratios” disclose three specific weight ratios of Component (b) to Component (a) for the disclosed mixture. For example, the first line of Table A1 discloses a mixture of Compound 22 with acibenzolar-S-methyl and lists weight ratios of acibenzolar-S-methyl to Compound 22 of 1:1, 1:4 or 1:17.

TABLE A1 Component (a) Component (b) Illustrative Ratios(*) Compound 22 acibenzolar-S-methyl 1:1 1:4  1:18 Compound 22 aldimorph 7:1 3:1 1:1 Compound 22 ametoctradin 3:1 1:1 1:3 Compound 22 amisulbrom 1:1 1:2 1:6 Compound 22 anilazine 22:1  8:1 4:1 Compound 22 azaconazole 2:1 1:2 1:4 Compound 22 azoxystrobin 3:1 1:1 1:3 Compound 22 benalaxyl 1:1 1:2 1:6 Compound 22 benalaxyl-M 1:1 1:3 1:8 Compound 22 benodanil 4:1 2:1 1:2 Compound 22 benomyl 11:1  4:1 1:1 Compound 22 benthiavalicarb 1:1 1:4  1:12 Compound 22 benthiavalicarb-isopropyl 1:1 1:4  1:12 Compound 22 bethoxazin 15:1  5:1 2:1 Compound 22 binapacryl 15:1  5:1 2:1 Compound 22 biphenyl 15:1  5:1 2:1 Compound 22 bitertanol 3:1 1:1 1:2 Compound 22 bixafen 2:1 1:1 1:3 Compound 22 blasticidin-S 1:4  1:12  1:30 Compound 22 Bordeaux mixture (tribasic copper sulfate) 45:1  15:1  5:1 Compound 22 boscalid 4:1 2:1 1:2 Compound 22 bromuconazole 3:1 1:1 1:3 Compound 22 bupirimate 1:3  1:10  1:30 Compound 22 captafol 15:1  5:1 2:1 Compound 22 captan 15:1  5:1 2:1 Compound 22 carbendazim 11:1  4:1 2:1 Compound 22 carboxin 4:1 2:1 1:2 Compound 22 carpropamid 3:1 1:1 1:3 Compound 22 chloroneb 100:1  35:1  14:1  Compound 22 chlorothalonil 15:1 5:1 2:1 Compound 22 chlozolinate 11:1 4:1 2:1 Compound 22 clotrimazole 3:1 1:1 1:3 Compound 22 copper hydroxide 45:1  15:1 5:1 Compound 22 copper oxychloride 45:1  15:1 5:1 Compound 22 cyazofamid 1:1 1:2 1:6 Compound 22 cyflufenamid 1:2 1:6  1:24 Compound 22 cymoxanil 1:1 1:2 1:5 Compound 22 cyproconazole 1:1 1:2 1:6 Compound 22 cyprodinil 4:1 2:1 1:2 Compound 22 dichlofluanid 15:1  5:1 2:1 Compound 22 diclocymet 15:1  5:1 2:1 Compound 22 diclomezine 3:1 1:1 1:3 Compound 22 dicloran 15:1  5:1 2:1 Compound 22 diethofencarb 7:1 2:1 1:2 Compound 22 difenoconazole 1:1 1:3  1:12 Compound 22 diflumetorim 15:1  5:1 2:1 Compound 22 dimethirimol 1:3 1:8  1:30 Compound 22 dimethomorph 3:1 1:1 1:2 Compound 22 dimoxystrobin 2:1 1:1 1:4 Compound 22 diniconazole 1:1 1:3 1:8 Compound 22 diniconazole-M 1:1 1:3  1:12 Compound 22 dinocap 2:1 1:1 1:3 Compound 22 dithianon 5:1 2:1 1:2 Compound 22 dodemorph 7:1 3:1 1:1 Compound 22 dodine 10:1  4:1 2:1 Compound 22 edifenphos 3:1 1:1 1:3 Compound 22 enestroburin 2:1 1:1 1:4 Compound 22 epoxiconazole 1:1 1:3 1:7 Compound 22 ethaboxam 2:1 1:1 1:3 Compound 22 ethirimol 7:1 3:1 1:1 Compound 22 etridiazole 7:1 2:1 1:2 Compound 22 famoxadone 2:1 1:1 1:4 Compound 22 fenamidone 2:1 1:1 1:4 Compound 22 fenarimol 1:2 1:7  1:24 Compound 22 fenbuconazole 1:1 1:3  1:10 Compound 22 fenfuram 4:1 1:1 1:2 Compound 22 fenhexamid 10:1  4:1 2:1 Compound 22 fenoxanil 15:1  4:1 1:1 Compound 22 fenpiclonil 15:1  5:1 2:1 Compound 22 fenpropidin 7:1 2:1 1:1 Compound 22 fenpropimorph 7:1 2:1 1:1 Compound 22 fenpyrazamine 3:1 1:1 1:3 Compound 22 fentin salt such as fentin acetate, fentin chloride or 3:1 1:1 1:3 fentin hydroxide Compound 22 ferbam 30:1  10:1  4:1 Compound 22 ferimzone 7:1 2:1 1:2 Compound 22 fluazinam 3:1 1:1 1:2 Compound 22 fludioxonil 2:1 1:1 1:4 Compound 22 flumetover 3:1 1:1 1:2 Compound 22 flumorph 3:1 1:1 1:3 Compound 22 fluopicolide 1:1 1:2 1:6 Compound 22 fluopyram 3:1 1:1 1:3 Compound 22 fluoroimide 37:1  14:1  5:1 Compound 22 fluoxastrobin 1:1 1:2 1:6 Compound 22 fluquinconazole 1:1 1:2 1:4 Compound 22 flusilazole 3:1 1:1 1:3 Compound 22 flusulfamide 15:1  5:1 2:1 Compound 22 flutianil 1:1 1:2 1:6 Compound 22 flutolanil 4:1 1:1 1:2 Compound 22 flutriafol 1:1 1:2 1:4 Compound 22 fluxapyroxad 2:1 1:1 1:3 Compound 22 folpet 15:1 5:1 2:1 Compound 22 fosetyl-aluminum 30:1  12:1  5:1 Compound 22 fuberidazole 11:1  4:1 2:1 Compound 22 furalaxyl 1:1 1:2 1:6 Compound 22 furametpyr 15:1 5:1 2:1 Compound 22 guazatine 15:1  5:1 2:1 Compound 22 hexaconazole 1:1 1:2 1:5 Compound 22 hymexazol 75:1  25:1  9:1 Compound 22 imazalil 1:1 1:2 1:5 Compound 22 imibenconazole 1:1 1:2 1:5 Compound 22 iminoctadine 15:1  4:1 1:1 Compound 22 iodocalb 15:1  5:1 2:1 Compound 22 ipconazole 1:1 1:2 1:5 Compound 22 iprobenfos 15:1  5:1 2:1 Compound 22 iprodione 15:1  5:1 2:1 Compound 22 iprovalicarb 2:1 1:1 1:3 Compound 22 isoprothiolane 45:1  15:1  5:1 Compound 22 isopyrazam 2:1 1:1 1:3 Compound 22 isotianil 2:1 1:1 1:3 Compound 22 kasugamycin 1:2 1:7  1:24 Compound 22 kresoxim-methyl 2:1 1:1 1:4 Compound 22 mancozeb 22:1  7:1 3:1 Compound 22 mandipropamid 2:1 1:1 1:4 Compound 22 maneb 22:1  7:1 3:1 Compound 22 mepanipyrim 6:1 2:1 1:1 Compound 22 mepronil 1:1 1:2 1:6 Compound 22 meptyldinocap 2:1 1:1 1:3 Compound 22 metalaxyl 1:1 1:2 1:6 Compound 22 metalaxyl-M 1:1 1:4  1:12 Compound 22 metconazole 1:1 1:2 1:6 Compound 22 methasulfocalb 15:1  5:1 2:1 Compound 22 metiram 15:1  5:1 2:1 Compound 22 metominostrobin 3:1 1:1 1:3 Compound 22 metrafenone 2:1 1:1 1:4 Compound 22 myclobutanil 1:1 1:3 1:8 Compound 22 naftifine 15:1  5:1 2:1 Compound 22 neo-asozin (ferric methanearsonate) 15:1  5:1 2:1 Compound 22 nuarimol 3:1 1:1 1:3 Compound 22 octhilinone 15:1  4:1 1:1 Compound 22 ofurace 1:1 1:2 1:6 Compound 22 orysastrobin 3:1 1:1 1:3 Compound 22 oxadixyl 1:1 1:2 1:6 Compound 22 oxolinic acid 7:1 2:1 1:2 Compound 22 oxpoconazole 1:1 1:2 1:5 Compound 22 oxycarboxin 4:1 1:1 1:2 Compound 22 oxytetracycline 3:1 1:1 1:3 Compound 22 pefurazoate 15:1  5:1 2:1 Compound 22 penconazole 1:2 1:6  1:15 Compound 22 pencycuron 11:1  4:1 2:1 Compound 22 penthiopyrad 2:1 1:1 1:3 Compound 22 phosphorous acid or a salt thereof 15:1  6:1 2:1 Compound 22 phthalide 15:1  6:1 2:1 Compound 22 picoxystrobin 1:1 1:2 1:5 Compound 22 piperalin 3:1 1:1 1:3 Compound 22 polyoxin 3:1 1:1 1:3 Compound 22 probenazole 3:1 1:1 1:3 Compound 22 prochloraz 7:1 2:1 1:2 Compound 22 procymidone 11:1  4:1 2:1 Compound 22 propamocarb or propamocarb-hydrochloride 10:1  4:1 2:1 Compound 22 propiconazole 1:1 1:2 1:5 Compound 22 propineb 11:1  4:1 2:1 Compound 22 proquinazid 1:1 1:3  1:12 Compound 22 prothiocarb 3:1 1:1 1:3 Compound 22 prothioconazole 1:1 1:2 1:5 Compound 22 pyraclostrobin 2:1 1:1 1:4 Compound 22 pyrametostrobin 2:1 1:1 1:4 Compound 22 pyraoxystrobin 2:1 1:1 1:4 Compound 22 pyrazophos 15:1  4:1 1:1 Compound 22 pyribencarb 4:1 1:1 1:2 Compound 22 pyributicarb 15:1  4:1 1:1 Compound 22 pyrifenox 3:1 1:1 1:3 Compound 22 pyrimethanil 3:1 1:1 1:2 Compound 22 pyriofenone 2:1 1:1 1:4 Compound 22 pyroquilon 3:1 1:1 1:3 Compound 22 pyrrolnitrin 15:1  5:1 2:1 Compound 22 quinomethionate 15:1  5:1 2:1 Compound 22 quinoxyfen 1:1 1:2 1:6 Compound 22 quintozene 15:1  5:1 2:1 Compound 22 silthiofam 2:1 1:1 1:4 Compound 22 simeconazole 1:1 1:2 1:5 Compound 22 spiroxamine 5:1 2:1 1:2 Compound 22 streptomycin 3:1 1:1 1:3 Compound 22 sulfur 75:1  25:1  9:1 Compound 22 tebuconazole 1:1 1:2 1:5 Compound 22 tebufloquin 3:1 1:1 1:3 Compound 22 tecloftalam 15:1  5:1 2:1 Compound 22 tecnazene 15:1  5:1 2:1 Compound 22 terbinafine 15:1  5:1 2:1 Compound 22 tetraconazole 1:1 1:2 1:5 Compound 22 thiabendazole 11:1  4:1 2:1 Compound 22 thifluzamide 3:1 1:1 1:3 Compound 22 thiophanate 11:1  4:1 2:1 Compound 22 thiophanate-methyl 11:1  4:1 2:1 Compound 22 thiram 37:1  14:1  5:1 Compound 22 tiadinil 2:1 1:1 1:3 Compound 22 tolclofos-methyl 37:1  14:1  5:1 Compound 22 tolylfluanid 15:1  5:1 2:1 Compound 22 triadimefon 1:1 1:2 1:5 Compound 22 triadimenol 1:1 1:2 1:5 Compound 22 triazoxide 15:1  5:1 2:1 Compound 22 tricyclazole 3:1 1:1 1:3 Compound 22 tridemorph 7:1 2:1 1:1 Compound 22 trifloxystrobin 2:1 1:1 1:4 Compound 22 triflumizole 3:1 1:1 1:3 Compound 22 triforine 3:1 1:1 1:3 Compound 22 trimorphamide 7:1 2:1 1:2 Compound 22 triticonazole 1:1 1:2 1:5 Compound 22 uniconazole 1:1 1:2 1:5 Compound 22 validamycin 3:1 1:1 1:3 Compound 22 valifenalate (valiphenal) 2:1 1:1 1:4 Compound 22 vinclozolin 15:1  6:1 2:1 Compound 22 zineb 37:1  14:1  5:1 Compound 22 ziram 37:1  14:1  5:1 Compound 22 zoxamide 2:1 1:1 1:4 Compound 22 5-chloro-6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin- 1:1 1:2 1:6 1-yl)[1,2,4]triazolo[1,5-a]pyrimidine Compound 22 Penflufen (N-[2-(1,3-dimethylbutyl)phenyl]-5-fluoro- 2:1 1:1 1:3 1,3-dimethyl-1H-pyrazole-4-carboxamide) Compound 22 N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3- 2:1 1:1 1:4 methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl) amino]butanamide Compound 22 N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-1-yl]oxy]-3- 2:1 1:1 1:4 methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl) amino]butanamide Compound 22 2-butoxy-6-iodo-3-propyl-4H-1-benzopyran-4-one 1:1 1:3  1:12 Compound 22 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl] 3:1 1:1 1:3 pyridine Compound 22 4-fluorophenyl N-[1-[[[1-(4-cyanophenyl)ethyl]sulfonyl] 2:1 1:1 1:4 methyl]propyl]carbamate Compound 22 N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)- 1:2 1:7  1:24 2,3-difluorophenyl]methylene]benzeneacetamide Compound 22 α-[methoxyimino]-N-methyl-2-[[[1-[3-(trifluoromethyl) 3:1 1:1 1:3 phenyl]ethoxy]imino]methyl]-benzeneacetamide Compound 22 N′-[4-[4-chloro-3-(trifluoromethyl)phenoxy]-2,5- 3:1 1:1 1:3 dimethylphenyl]-N-ethyl-N-methylmethanimidamide Compound 22 N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methyl- 3:1 1:1 1:3 benzenesulfonamide Compound 22 2-[[[3-(2,6-dichlorophenyl)-1-methyl-2-propen-1- 3:1 1:1 1:3 ylidene]amino]oxy]methyl]-α-(methoxyimino)-N- methylbenzeneacetamide Compound 22 pentyl N-[4-[[[[(1-methyl-1H-tetrazol-5-yl)phenyl- 3:1 1:1 1:3 methylene]amino]oxy]methyl]-2-thiazolyl]carbamate Compound 22 pentyl N-[6-[[[[(1-methyl-1H-tetrazol-5-yl)phenyl- 3:1 1:1 1:3 methylene]amino]oxy]methyl]-2-pyridinyl]carbamate (*) Ratios of Component (b) relative to Component (a) by weight.

Tables A2 through A54 are each constructed the same as Table A1 above except that entries below the “Component (a)” column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table A2 the entries below the “Component (a)” column heading all recite “Compound 18”, and the first line below the column headings in Table A2 specifically discloses a mixture of Compound 18 with acibenzolar-S-methyl. Tables A3 through A54 are constructed similarly.

Table Number Component (a) Column Entries A2 Compound 18 A3 Compound 23 A4 Compound 24 A5 Compound 36 A6 Compound 41 A7 Compound 45 A8 Compound 87 A9 Compound 91 A10 Compound 118 A11 Compound 139 A12 Compound 148 A13 Compound 172 A14 Compound 175 A15 Compound 193 A16 Compound 232 A17 Compound 265 A18 Compound 266 A19 Compound 284 A20 Compound 286 A21 Compound 287 A22 Compound 292 A23 Compound 297 A24 Compound 332 A25 Compound 336 A26 Compound 343 A27 Compound 346 A28 Compound 349 A29 Compound 351 A30 Compound 352 A31 Compound 357 A32 Compound 358 A33 Compound 360 A34 Compound 361 A35 Compound 364 A36 Compound 365 A37 Compound 367 A38 Compound 368 A39 Compound 369 A40 Compound 372 A41 Compound 373 A42 Compound 374 A43 Compound 375 A44 Compound 376 A45 Compound 377 A46 Compound 378 A47 Compound 379 A48 Compound 380 A49 Compound 381 A50 Compound 382 A51 Compound 383 A52 Compound 384 A53 Compound 385 A54 Compound 386

Table B1 lists specific combinations of a Component (b) compound with Component (a) illustrative of the mixtures, compositions and methods of the present invention. The first column of Table B1 lists the specific Component (b) compound (e.g., “acibenzolar-S-methyl” in the first line). The second, third and fourth columns of Table B1 lists ranges of weight ratios for rates at which the Component (b) compound is typically applied to a field-grown crop relative to Component (a) (e.g., “2:1 to 1:180” of acibenzolar-S-methyl relative to Component (a) by weight). Thus, for example, the first line of Table B1 specifically discloses the combination of acibenzolar-S-methyl with Component (a) is typically applied in a weight ratio between 2:1 to 1:180. The remaining lines of Table B1 are to be construed similarly. Table B1 thus supplements the specific ratios disclosed in Tables A1 through A54 with ranges of ratios for these combinations.

TABLE B1 More Most Typical Typical Typical Weight Weight Weight Component (b) Ratio Ratio Ratio acibenzolar-S-methyl   2:1 to 1:180   1:1 to 1:60   1:1 to 1:18 aldimorph  30:1 to 1:3  10:1 to 1:1   7:1 to 1:1 ametoctradin   9:1 to 1:18   3:1 to 1:6   3:1 to 1:3 amisulbrom   6:1 to 1:18   2:1 to 1:6   1:1 to 1:6 anilazine  90:1 to 2:1  30:1 to 4:1  22:1 to 4:1 azaconazole   7:1 to 1:18   2:1 to 1:6   2:1 to 1:4 azoxystrobin   9:1 to 1:12   3:1 to 1:4   3:1 to 1:3 benalaxyl   4:1 to 1:18   1:1 to 1:6   1:1 to 1:6 benalaxyl-M   4:1 to 1:36   1:1 to 1:12   1:1 to 1:8 benodanil  18:1 to 1:6   6:1 to 1:2   4:1 to 1:2 benomyl  45:1 to 1:4  15:1 to 1:1  11:1 to 1:1 benthiavalicarb or   2:1 to 1:36   1:1 to 1:12   1:1 to 1:12 benthiavalicarb-     isopropyl     bethoxazin 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 binapacryl 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 biphenyl 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 bitertanol  15:1 to 1:5   5:1 to 1:2   3:1 to 1:2 bixafen  12:1 to 1:9   4:1 to 1:3   2:1 to 1:3 blasticidin-S   3:1 to 1:90   1:1 to 1:30   1:4 to 1:30 boscalid  18:1 to 1:6   6:1 to 1:2   4:1 to 1:2 bromuconazole  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 bupirimate   3:1 to 1:90  1:1 to 1:30   1:3 to 1:30 captafol  90:1 to 1:4  30:1 to 1:2  15:1 to 2:1 captan  90:1 to 1:4  30:1 to 1:2  15:1 to 2:1 carbendazim  45:1 to 1:4  15:1 to 1:2  11:1 to 2:1 carboxin  18:1 to 1:6   6:1 to 1:2   4:1 to 1:2 carpropamid  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 chloroneb 300:1 to 2:1 100:1 to 4:1 100:1 to 14:1 chlorothalonil  90:1 to 1:4  30:1 to 1:2  15:1 to 2:1 chlozolinate  45:1 to 1:2  15:1 to 2:1  11:1 to 2:1 clotrimazole  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 copper salts such as 450:1 to 1:1 150:1 to 4:1  45:1 to 5:1 Bordeaux mixture (tribasic copper sulfate), copper oxychloride, copper sulfate and copper hydroxide cyazofamid  4:1 to 1:18  1:1 to 1:6  1:1 to 1:6 cyflufenamid  1:1 to 1:90  1:2 to 1:30  1:2 to 1:24 cymoxanil  6:1 to 1:18  2:1 to 1:6  1:1 to 1:5 cyproconazole  4:1 to 1:18  1:1 to 1:6  1:1 to 1:6 cyprodinil  22:1 to 1:9  7:1 to 1:3  4:1 to 1:2 dichlofluanid 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 diclocymet 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 diclomezine  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 dicloran 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 diethofencarb  22:1 to 1:9   7:1 to 1:3   7:1 to 1:2 difenoconazole   4:1 to 1:36   1:1 to 1:12   1:1 to 1:12 diflumetorim 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 dimethirimol   3:1 to 1:90   1:1 to 1:30   1:3 to 1:30 dimethomorph   9:1 to 1:6   3:1 to 1:2   3:1 to 1:2 dimoxystrobin   9:1 to 1:18   3:1 to 1:6   2:1 to 1:4 diniconazole   3:1 to 1:36   1:1 to 1:12   1:1 to 1:8 diniconazole M   3:1 to 1:90   1:1 to 1:30   1:1 to 1:12 dinocap   7:1 to 1:9   2:1 to 1:3   2:1 to 1:3 dithianon  15:1 to 1:4   5:1 to 1:2   5:1 to 1:2 dodemorph  30:1 to 1:3  10:1 to 1:1   7:1 to 1:1 dodine  30:1 to 1:2  10:1 to 2:1  10:1 to 2:1 edifenphos  30:1 to 1:9  10:1 to 1:3   3:1 to 1:3 enestroburin   9:1 to 1:18   3:1 to 1:6   2:1 to 1:4 epoxiconazole   3:1 to 1:36   1:1 to 1:12   1:1 to 1:7 ethaboxam   7:1 to 1:9   2:1 to 1:3   2:1 to 1:3 ethirimol  30:1 to 1:3  10:1 to 1:1   7:1 to 1:1 etridiazole  30:1 to 1:9  10:1 to 1:3   7:1 to 1:2 famoxadone   9:1 to 1:18   3:1 to 1:6   2:1 to 1:4 fenamidone   6:1 to 1:18   2:1 to 1:6   2:1 to 1:4 fenarimol   3:1 to 1:90   1:1 to 1:30   1:2 to 1:24 fenbuconazole   3:1 to 1:30   1:1 to 1:10   1:1 to 1:10 fenfuram  18:1 to 1:6   6:1 to 1:2   4:1 to 1:2 fenhexamid  30:1 to 1:2  10:1 to 2:1  10:1 to 2:1 fenoxanil 150:1 to 1:36  50:1 to 1:12  15:1 to 1:1 fenpiclonil  75:1 to 1:9  25:1 to 1:3  15:1 to 2:1 fenpropidin  30:1 to 1:3  10:1 to 1:1   7:1 to 1:1 fenpropimorph  30:1 to 1:3  10:1 to 1:1   7:1 to 1:1 fenpyrazamine 100:1 to 1:100  10:1 to 1:10   3:1 to 1:3 fentin salt such as the  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 acetate, chloride or hydroxide ferbam 300:1 to 1:2 100:1 to 2:1  30:1 to 4:1 ferimzone  30:1 to 1:5  10:1 to 1:2   7:1 to 1:2 fluazinam  22:1 to 1:5   7:1 to 1:2   3:1 to 1:2 fludioxonil   7:1 to 1:12   2:1 to 1:4   2:1 to 1:4 flumetover   9:1 to 1:6   3:1 to 1:2   3:1 to 1:2 flumorph   9:1 to 1:18   3:1 to 1:6   3:1 to 1:3 fluopicolide   3:1 to 1:18   1:1 to 1:6   1:1 to 1:6 fluopyram  15:1 to 1:90   5:1 to 1:30   3:1 to 1:3 fluoromide 150:1 to 2:1  50:1 to 4:1  37:1 to 5:1 fluoxastrobin   4:1 to 1:18   1:1 to 1:6   1:1 to 1:6 fluquinconazole   4:1 to 1:12   1:1 to 1:4   1:1 to 1:4 flusilazole  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 flusulfamide  90:1 to 1:2  30:1 to 2:1  15:1 to 2:1 flutianil   7:1 to 1:36   2:1 to 1:12   1:1 to 1:6 flutolanil  18:1 to 1:6   6:1 to 1:2   4:1 to 1:2 flutriafol   4:1 to 1:12   1:1 to 1:4   1:1 to 1:4 fluxapyroxad  12:1 to 1:9   4:1 to 1:3   2:1 to 1:3 folpet  90:1 to 1:4  30:1 to 1:2  15:1 to 2:1 fosetyl-aluminum 225:1 to 2:1  75:1 to 5:1  30:1 to 5:1 fuberidazole  45:1 to 1:4  15:1 to 1:2  11:1 to 2:1 furalaxyl  15:1 to 1:45   5:1 to 1:15   1:1 to 1:6 furametpyr 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 guazatine or iminoctadine 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 hexaconazole  15:1 to 1:36   5:1 to 1:12   1:1 to 1:5 hymexazol 225:1 to 2:1  75:1 to 4:1  75:1 to 9:1 imazalil  7:1 to 1:18   2:1 to 1:6   1:1 to 1:5 imibenconazole  15:1 to 1:36   5:1 to 1:12   1:1 to 1:5 iodocarb 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 ipconazole  15:1 to 1:36   5:1 to 1:12   1:1 to 1:5 iprobenfos 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 iprodione 120:1 to 1:2  40:1 to 2:1  15:1 to 2:1 iprovalicarb  9:1 to 1:9   3:1 to 1:3   2:1 to 1:3 isoprothiolane 150:1 to 2:1  50:1 to 4:1  45:1 to 5:1 isopyrazam  12:1 to 1:9   4:1 to 1:3   2:1 to 1:3 isotianil  12:1 to 1:9   4:1 to 1:3   2:1 to 1:3 kasugamycin  7:1 to 1:90   2:1 to 1:30   1:2 to 1:24 kresoxim-methyl  7:1 to 1:18   2:1 to 1:6   2:1 to 1:4 mancozeb 180:1 to 1:3  60:1 to 2:1  22:1 to 3:1 mandipropamid  6:1 to 1:18   2:1 to 1:6  2:1 to 1:4 maneb 180:1 to 1:3  60:1 to 2:1  22:1 to 3:1 mepanipyrim  18:1 to 1:3  6:1 to 1:1  6:1 to 1:1 mepronil  7:1 to 1:36  2:1 to 1:12  1:1 to 1:6 meptyldinocap  7:1 to 1:9  2:1 to 1:3  2:1 to 1:3 metalaxyl  15:1 to 1:45  5:1 to 1:15  1:1 to 1:6 metalaxyl-M  7:1 to 1:90  2:1 to 1:30  1:1 to 1:12 metconazole  3:1 to 1:18  1:1 to 1:6  1:1 to 1:6 methasulfocarb 150:1 to 1:36  50:1 to 1:12  15:1 to 1:1 metiram 150:1 to 1:36  50:1 to 1:12  15:1 to 1:1 metominostrobin   9:1 to 1:12   3:1 to 1:4   3:1 to 1:3 metrafenone   6:1 to 1:12   2:1 to 1:4   2:1 to 1:4 myclobutanil   5:1 to 1:26  1:1 to 1:9   1:1 to 1:8 naftifine 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 neo-asozin (ferric 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 methanearsonate) nuarimol  15:1 to 1:9  5:1 to 1:3  3:1 to 1:3 octhilinone 150:1 to 1:36  50:1 to 1:12  15:1 to 1:1 ofurace  15:1 to 1:45   5:1 to 1:15   1:1 to 1:6 orysastrobin   9:1 to 1:12   3:1 to 1:4   3:1 to 1:3 oxadixyl  15:1 to 1:45   5:1 to 1:15   1:1 to 1:6 oxolinic acid  30:1 to 1:9  10:1 to 1:3   7:1 to 1:2 oxpoconazole  15:1 to 1:36   5:1 to 1:12   1:1 to 1:5 oxycarboxin  18:1 to 1:6   6:1 to 1:2   4:1 to 1:2 oxytetracycline  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 pefurazoate 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 penconazole  1:1 to 1:45  1:2 to 1:15  1:2 to 1:15 pencycuron 150:1 to 1:2  50:1 to 2:1  11:1 to 2:1 penthiopyrad  12:1 to 1:9   4:1 to 1:3   2:1 to 1:3 phosphorous acid 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 and salts thereof     phthalide 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 picoxystrobin   7:1 to 1:18   2:1 to 1:6   1:1 to 1:5 piperalin  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 polyoxin  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 probenazole  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 prochloraz  22:1 to 1:4   7:1 to 1:1   7:1 to 1:2 procymidone  45:1 to 1:3  15:1 to 1:1  11:1 to 2:1 propamocarb or  30:1 to 1:2  10:1 to 2:1  10:1 to 2:1 propamocarb- hydrochloride propiconazole  4:1 to 1:18  1:1 to 1:6  1:1 to 1:5 propineb  45:1 to 1:2  15:1 to 2:1  11:1 to 2:1 proquinazid  3:1 to 1:36  1:1 to 1:12  1:1 to 1:12 prothiocarb  9:1 to 1:18  3:1 to 1:6  3:1 to 1:3 prothioconazole  6:1 to 1:18  2:1 to 1:6  1:1 to 1:5 pyraclostrobin  9:1 to 1:18  3:1 to 1:6  2:1 to 1:4 pyrametostrobin  9:1 to 1:18  3:1 to 1:6  2:1 to 1:4 pyraoxystrobin  9:1 to 1:18  3:1 to 1:6  2:1 to 1:4 pyrazophos 150:1 to 1:36  50:1 to 1:12  15:1 to 1:1 pyribencarb  15:1 to 1:6  5:1 to 1:2  4:1 to 1:2 pyrifenox  15:1 to 1:9  5:1 to 1:3  3:1 to 1:3 pyrimethanil  30:1 to 1:6  10:1 to 1:2  3:1 to 1:2 pyriofenone  6:1 to 1:12   2:1 to 1:4  2:1 to 1:4 pyroquilon  15:1 to 1:9   5:1 to 1:3  3:1 to 1:3 pyrrolnitrin 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 quinmethionate 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 quinoxyfen  4:1 to 1:18   1:1 to 1:6   1:1 to 1:6 quintozene 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 silthiofam   7:1 to 1:18   2:1 to 1:6  2:1 to 1:4 simeconazole  15:1 to 1:36   5:1 to 1:12  1:1 to 1:5 spiroxamine  22:1 to 1:4   7:1 to 1:2  5:1 to 1:2 streptomycin  15:1 to 1:9   5:1 to 1:3  3:1 to 1:3 sulfur 300:1 to 3:1 100:1 to 9:1  75:1 to 9:1 tebuconazole  7:1 to 1:18   2:1 to 1:6   1:1 to 1:5 tebufloquin 100:1 to 1:100  10:1 to 1:10   3:1 to 1:3 tecloftalam 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 tecnazene 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 terbinafine 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 tetraconazole  15:1 to 1:36  5:1 to 1:12  1:1 to 1:5 thiabendazole  45:1 to 1:4  15:1 to 1:2  11:1 to 2:1 thifluzamide  15:1 to 1:9   5:1 to 1:3   3:1 to 1:3 thiophanate  45:1 to 1:3  15:1 to 2:1  11:1 to 2:1 thiophanate-methyl  45:1 to 1:3  15:1 to 2:1  11:1 to 2:1 thiram 150:1 to 1:2  50:1 to 2:1  37:1 to 5:1 tiadinil  12:1 to 1:9  4:1 to 1:3  2:1 to 1:3 tolclofos-methyl 150:1 to 1:2  50:1 to 2:1  37:1 to 5:1 tolylfluanid 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 triadimefon  15:1 to 1:36  5:1 to 1:12  1:1 to 1:5 triadimenol  15:1 to 1:36  5:1 to 1:12  1:1 to 1:5 triazoxide 150:1 to 1:36  50:1 to 1:12  15:1 to 2:1 tricyclazole  15:1 to 1:9   5:1 to 1:3  3:1 to 1:3 tridemorph  30:1 to 1:3  10:1 to 1:1  7:1 to 1:1 trifloxystrobin   6:1 to 1:18   2:1 to 1:6  2:1 to 1:4 triflumizole  15:1 to 1:9   5:1 to 1:3  3:1 to 1:3 triforine  15:1 to 1:9   5:1 to 1:3  3:1 to 1:3 trimorphamide  45:1 to 1:9  15:1 to 1:3  7:1 to 1:2 triticonazole  15:1 to 1:36   5:1 to 1:12  1:1 to 1:5 uniconazole  15:1 to 1:36   5:1 to 1:12  1:1 to 1:5 validamycin 150:1 to 1:36  50:1 to 1:12  3:1 to 1:3 valifenalate (valiphenal)  6:1 to 1:18   2:1 to 1:6  2:1 to 1:4 vinclozolin 120:1 to 1:2  40:1 to 2:1  15:1 to 2:1 zineb 150:1 to 1:2  50:1 to 2:1  37:1 to 5:1 ziram 150:1 to 1:2  50:1 to 2:1  37:1 to 5:1 zoxamide  6:1 to 1:18   2:1 to 1:6  2:1 to 1:4 5-chloro-6-(2,4,6-  15:1 to 1:36   5:1 to 1:12  1:1 to 1:6 trifluorophenyl)-7-(4- methylpiperidin-1- yl)[1,2,4]triazolo[1,5- a]pyrimidine penflufen (N-[2-(1,3-  12:1 to 1:9   4:1 to 1:3   2:1 to 1:3 dimethylbutyl)phenyl]- 5-fluoro-1,3- dimethyl-1H-pyrazole- 4-carboxamide) N-[2-[4-[[3-(4-  6:1 to 1:18  2:1 to 1:6  2:1 to 1:4 chlorophenyl)-2-propyn-1- yl]oxy]-3- methoxyphenyl]ethyl]- 3-methyl- 2-[methylsulfonyl)ami- no]butanamide N-[2-[4-[[3-(4-  6:1 to 1:18  2:1 to 1:6  2:1 to 1:4 chlorophenyl)-2-propyn-1- yl]oxy]-3- methoxyphenyl]ethyl]- 3-methyl- 2-[(ethylsulfonyl)ami- no]butanamide 2-butoxy-6-iodo-  3:1 to 1:36  1:1 to 1:12  1:1 to 1:12 3-propyl-4H-1- benzopyran-4-one 3-[5-(4-chlorophenyl)-  15:1 to 1:9  5:1 to 1:3  3:1 to 1:3 2,3-dimethyl-3- isoxazolidinyl]pyridine 4-fluorophenyl N-[1-[[[1-(4-  6:1 to 1:18  2:1 to 1:6  2:1 to 1:4 cyanophenyl)ethyl]sul- fonyl]methyl]propyl] carbamate N-[[(cyclopropyl-  1:1 to 1:90  1:2 to 1:30  1:2 to 1:24 methoxy)amino][6- (difluoromethoxy)-2,3- difluorophenyl]me- thylene]benzene- acetamide α-[methoxyimino]-N-  9:1 to 1:18  3:1 to 1:6  3:1 to 1:3 methyl-2-[[[1-[3- (trifluoromethyl)phe- nyl]ethoxy]imino]- methyl]benzeneacetamide N′-[4-[4-chloro-3-  15:1 to 1:18   5:1 to 1:6   3:1 to 1:3 (trifluoromethyl)phenoxy]- 2,5-dimethylphenyl]- N-ethyl-N- methylmethanimidamide N-(4-chloro-2-  15:1 to 1:18   5:1 to 1:6   3:1 to 1:3 nitrophenyl)-N-ethyl-4- methylbenzenesulfonamide 2-[[[3-(2,6-dichlorophenyl)-  9:1 to 1:18  3:1 to 1:6  3:1 to 1:3 1-methyl-2- propen-1-ylidene]ami- no]oxy]methyl]-α- (methoxyimino)-N- methylbenzeneacetamide pentyl N-[4-[[[[(1-methyl-  9:1 to 1:18  3:1 to 1:6  3:1 to 1:3 1H-tetrazol-5- yl)phenylmethy- lene]amino]oxy]methyl]-2- thiazolyl]carbamate pentyl N-[6-[[[[(1-methyl-  9:1 to 1:18  3:1 to 1:6  3:1 to 1:3 1H-tetrazol-5- yl)phenylmethylene]ami- no]oxy]methyl]-2- pyridinyl]carbamate

As already noted, the present invention includes embodiments wherein in the composition comprising components (a) and (b), component (b) comprises at least one fungicide from each of two groups selected from (b1) through (b46). Tables C1 through C54 list specific mixtures (compound numbers refer to compounds in Index Table A) to illustrate embodiments wherein component (b) includes at least one fungicide from each of two groups selected from (b1) through (b46). In Table C1, each line below the column headings “Component (a)” and “Component (b)” specifically discloses a mixture of Component (a), which is Compound 22, with at least two Component (b) fungicides. The entries under the heading “Illustrative Ratios” disclose three specific weight ratios of Component (a) to each Component (b) fungicide in sequence for the disclosed mixture. For example, the first line discloses a mixture of Compound 22 with cyproconazole and azoxystrobin and lists weight ratios of Compound 22 to cyproconazole to azoxystrobin of 1:1:1, 2:1:1 or 3:1:1.

TABLE C1 Component (a) Component (b) Illustrative Ratios(*) Compound 22 cyproconazole azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole bixafen 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole boscalid 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 cyproconazole fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 cyproconazole sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 cyproconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 cyproconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 difenconazole azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole bixafen 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole boscalid 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 difenconazole fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 difenconazole sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 difenconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 difenconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 epoxiconazole azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole bixafen 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole boscalid 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 epoxiconazole fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 epoxiconazole sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 epoxiconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 epoxiconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 metconazole azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 metconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 metconazole picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 metconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 metconazole trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 metconazole bixafen 1:1:2 2:1:2 3:1:2 Compound 22 metconazole boscalid 1:1:2 2:1:2 3:1:2 Compound 22 metconazole cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 metconazole fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 metconazole isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 metconazole metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 metconazole penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 metconazole proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 metconazole quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 metconazole sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 metconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 metconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 myclobutanil azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil bixafen 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil boscalid 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 myclobutanil fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 myclobutanil sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 myclobutanil picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 myclobutanil trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 prothioconazole azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole bixafen 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole boscalid 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 prothioconazole fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 prothioconazole sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 prothioconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 prothioconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 tebuconazole azoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole kresoxim-methyl 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole picoxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole pyraclostrobin 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole trifloxystrobin 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole bixafen 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole boscalid 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole cyflufenamid 1:2:1 2:2:1 3:2:1 Compound 22 tebuconazole fluopyram 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole isopyrazam 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole metrafenone 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole penthiopyrad 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole proquinazid 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole quinoxyfen 1:1:1 2:1:1 3:1:1 Compound 22 tebuconazole sedaxane 1:1:2 2:1:2 3:1:2 Compound 22 tebuconazole picoxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 Compound 22 tebuconazole trifloxystrobin proquinazid 1:1:1:1 2:1:1:1 3:1:1:1 (*) Ratios of Component (a) relative to Component (b) in sequence, by weight.

Tables C2 through C54 are each constructed the same as Table C1 above except that entries below the “Component (a)” column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table C2 the entries below the “Component (a)” column heading all recite “Compound 18”, and the first line in below the column headings in Table C2 specifically discloses a mixture of Compound 18 with cyproconazole and azoxystrobin, and the illustrative weight ratios of 1:1:1, 2:1:1 and 3:1:1 of Compound 18:cyproconazole:azoxystrobin. Tables C3 through C54 are constructed similarly.

Table Number Component (a) Column Entries C2 Compound 18 C3 Compound 23 C4 Compound 24 C5 Compound 36 C6 Compound 41 C7 Compound 45 C8 Compound 87 C9 Compound 91 C10 Compound 118 C11 Compound 139 C12 Compound 148 C13 Compound 172 C14 Compound 175 C15 Compound 193 C16 Compound 232 C17 Compound 265 C18 Compound 266 C19 Compound 284 C20 Compound 286 C21 Compound 287 C22 Compound 292 C23 Compound 297 C24 Compound 332 C25 Compound 336 C26 Compound 343 C27 Compound 346 C28 Compound 349 C29 Compound 351 C30 Compound 352 C31 Compound 357 C32 Compound 358 C33 Compound 360 C34 Compound 361 C35 Compound 364 C36 Compound 365 C37 Compound 367 C38 Compound 368 C39 Compound 369 C40 Compound 372 C41 Compound 373 C42 Compound 374 C43 Compound 375 C44 Compound 376 C45 Compound 377 C46 Compound 378 C47 Compound 379 C48 Compound 380 C49 Compound 381 C50 Compound 382 C51 Compound 383 C52 Compound 384 C53 Compound 385 C54 Compound 386

As mentioned in the Summary of the Invention, one aspect of the present invention is a composition comprising (i.e. a mixture or combination of) a compound of Formula 1, an N-oxide, or a salt thereof, and at least one invertebrate pest control compound or agent (e.g., insecticide, acaricide). Of note is a composition comprising component (a) and at least one (i.e. one or more) invertebrate pest control compound or agent, which then can be subsequently combined with component (b) to provide a composition comprising components (a) and (b) and the one or more invertebrate pest control compounds or agents. Alternatively without first mixing with component (b), a biologically effective amount of the composition comprising component (a) with at least one invertebrate pest control agent can be applied to a plant or plant seed (directly or through the environment of the plant or plant seed) to protect the plant or plant seed from diseases caused by fungal pathogens and injury caused by invertebrate pests.

For embodiments where one or more of invertebrate pest control compounds are used, the weight ratio of these compounds (in total) to the component (a) compounds is typically between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (for example ratios between about 1:30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity.

Of note is a composition of the present invention which comprises in addition to a component (a) compound, alone or in combination with fungicidal component (b), at least one invertebrate pest control compound or agent selected from the group consisting of abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole, chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, meperfluthrin, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulfoxaflor, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethylfluthin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, nucleopolyhedro viruses, encapsulated delta-endotoxins of Bacillus thuringiensis, baculoviruses, entomopathogenic bacteria, entomopathogenic viruses and entomopathogenic fungi.

In certain instances, combinations of a compound of Formula 1 or an N-oxide or salt thereof (i.e. component (a)), alone or in mixture with fungicidal component (b), with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of invertebrate pest control active ingredients occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load.

Table D1 lists specific combinations of invertebrate pest control agents with Compound 22 (identified in Index Table A) as a component (a) compound illustrative of mixtures and compositions comprising these active ingredients and methods using them according to the present invention. The second column of Table D1 lists the specific invertebrate pest control agents (e.g., “Abamectin” in the first line). The third column of Table D1 lists the mode of action (if known) or chemical class of the invertebrate pest control agents. The fourth column of Table D1 lists embodiment(s) of ranges of weight ratios for rates at which the invertebrate pest control agent is typically applied relative to Compound 22 alone or in combination with fungicidal component (b) (e.g., “50:1 to 1:50” of abamectin relative to a Compound 22 by weight). Thus, for example, the first line of Table D1 specifically discloses the combination of Compound 22 with abamectin is typically applied in a weight ratio between 50:1 to 1:50. The remaining lines of Table D1 are to be construed similarly

TABLE D1 Invertebrate Mode of Action Typical Component Pest Control or Chemical Weight (a) Agent Class Ratio Compound 22 Abamectin macrocyclic lactones   50:1 to 1:50 Compound 22 Acetamiprid neonicotinoids  150:1 to 1:200 Compound 22 Amitraz octopamine receptor  200:1 to 1:100 ligands Compound 22 Avermectin macrocyclic lactones   50:1 to 1:50 Compound 22 Azadirachtin ecdysone agonists  100:1 to 1:120 Compound 22 Beta-cyfluthrin sodium channel  150:1 to 1:200 modulators Compound 22 Bifenthrin sodium channel  100:1 to 1:10 modulators Compound 22 Buprofezin chitin synthesis  500:1 to 1:50 inhibitors Compound 22 Cartap nereistoxin analogs  100:1 to 1:200 Compound 22 Chloran- ryanodine receptor  100:1 to 1:120 traniliprole ligands Compound 22 Chlorfenapyr mitochondrial electron  300:1 to 1:200 transport inhibitors   Compound 22 Chlorpyrifos cholinesterase  500:1 to 1:200 inhibitors Compound 22 Clothianidin neonicotinoids  100:1 to 1:400 Compound 22 Cyantrani- ryanodine receptor  100:1 to 1:120 liprole ligands Compound 22 Cyfluthrin sodium channel  150:1 to 1:200 modulators Compound 22 Cyhalothrin sodium channel  150:1 to 1:200 modulators Compound 22 Cypermethrin sodium channel  150:1 to 1:200 modulators Compound 22 Cyromazine chitin synthesis  400:1 to 1:50 inhibitors Compound 22 Deltamethrin sodium channel   50:1 to 1:400 modulators Compound 22 Dieldrin cyclodiene insecticides  200:1 to 1:100 Compound 22 Dinotefuran neonicotinoids  150:1 to 1:200 Compound 22 Diofenolan molting inhibitor  150:1 to 1:200 Compound 22 Emamectin macrocyclic lactones   50:1 to 1:10 Compound 22 Endosulfan cyclodiene insecticides  200:1 to 1:100 Compound 22 Esfenvalerate sodium channel  100:1 to 1:400 modulators Compound 22 Ethiprole GABA-regulated  200:1 to 1:100 chloride channel blockers Compound 22 Fenothiocarb  150:1 to 1:200 Compound 22 Fenoxycarb juvenile hormone  500:1 to 1:100 mimics Compound 22 Fenvalerate sodium channel  150:1 to 1:200 modulators Compound 22 Fipronil GABA-regulated  150:1 to 1:100 chloride channel   blockers   Compound 22 Flonicamid  200:1 to 1:100 Compound 22 Flubendiamide ryanodine receptor  100:1 to 1:120 ligands   Compound 22 Flufenoxuron chitin synthesis  200:1 to 1:100 inhibitors   Compound 22 Hexaflumuron chitin synthesis  300:1 to 1:50 inhibitors   Compound 22 Hydra- mitochondrial  150:1 to 1:250 methylnon electron transport   inhibitors   Compound 22 Imidacloprid neonicotinoids 1000:1 to 1:1000   Compound 22 Indoxacarb sodium channel  200:1 to 1:50 modulators   Compound 22 Lambda- sodium channel   50:1 to 1:250 cyhalothrin modulators Compound 22 Lufenuron chitin synthesis  500:1 to 1:250 inhibitors Compound 22 Meperfluthrin Sodium channel  100:1 to 1:400 modulators Compound 22 Metaflumizone  200:1 to 1:200 Compound 22 Methomyl cholinesterase  500:1 to 1:100 inhibitors Compound 22 Methoprene juvenile hormone  500:1 to 1:100 mimics Compound 22 Methoxy- ecdysone agonists   50:1 to 1:50 fenozide Compound 22 Nitenpyram neonicotinoids  150:1 to 1:200 Compound 22 Nithiazine neonicotinoids  150:1 to 1:200 Compound 22 Novaluron chitin synthesis  500:1 to 1:150 inhibitors Compound 22 Oxamyl cholinesterase  200:1 to 1:200 inhibitors Compound 22 Pymetrozine  200:1 to 1:100 Compound 22 Pyrethrin sodium channel  100:1 to 1:10 modulators Compound 22 Pyridaben mitochondrial  200:1 to 1:100 electron transport inhibitors Compound 22 Pyridalyl  200:1 to 1:100 Compound 22 Pyriproxyfen juvenile hormone  500:1 to 1:100 mimics Compound 22 Ryanodine ryanodine receptor  100:1 to 1:120 ligands Compound 22 Spinetoram macrocyclic lactones  150:1 to 1:100 Compound 22 Spinosad macrocyclic lactones  500:1 to 1:10 Compound 22 Spirodiclofen lipid biosynthesis  200:1 to 1:200 inhibitors Compound 22 Spiromesifen lipid biosynthesis  200:1 to 1:200 inhibitors Compound 22 Sulfoxaflor  200:1 to 1: 200 Compound 22 Tebufenozide ecdysone agonists  500:1 to 1:250 Compound 22 Tetramethyl- Sodium channel  100:1 to 1:400 fluthrin modulators Compound 22 Thiacloprid neonicotinoids  100:1 to 1:200 Compound 22 Thiamethoxam neonicotinoids 1250:1 to 1:1000 Compound 22 Thiodicarb cholinesterase  500:1 to 1:400 inhibitors Compound 22 Thiosultap-  150:1 to 1:100 sodium Compound 22 Tralomethrin sodium channel  150:1 to 1:200 modulators Compound 22 Triazamate cholinesterase  250:1 to 1:100 inhibitors Compound 22 Triflumuron chitin synthesis  200:1 to 1:100 inhibitors Compound 22 Bacillus biological agents  50:1 to 1:10 thuringiensis Compound 22 Bacillus biological agents  50:1 to 1:10 thuringiensis delta-endotoxin Compound 22 NPV (e.g., biological agents  50:1 to 1:10 Gemstar)

Tables D2 through D54 are each constructed the same as Table D1 above except that entries below the “Component (a)” column heading are replaced with the respective Component (a) Column Entry shown below. Thus, for example, in Table D2 the entries below the “Component (a)” column heading all recite “Compound 18”, and the first line in below the column headings in Table D2 specifically discloses a mixture of Compound 18 with abamectin. Tables D3 through D54 are constructed similarly.

Table Number Component (a) Column Entries D2 Compound 18 D3 Compound 23 D4 Compound 24 D5 Compound 36 D6 Compound 41 D7 Compound 45 D8 Compound 87 D9 Compound 91 D10 Compound 118 D11 Compound 139 D12 Compound 148 D13 Compound 172 D14 Compound 175 D15 Compound 193 D16 Compound 232 D17 Compound 265 D18 Compound 266 D19 Compound 284 D20 Compound 286 D21 Compound 287 D22 Compound 292 D23 Compound 297 D24 Compound 332 D25 Compound 336 D26 Compound 343 D27 Compound 346 D28 Compound 349 D29 Compound 351 D30 Compound 352 D31 Compound 357 D32 Compound 358 D33 Compound 360 D34 Compound 361 D35 Compound 364 D35 Compound 365 D37 Compound 367 D38 Compound 368 D39 Compound 369 D40 Compound 372 D41 Compound 373 D42 Compound 374 D43 Compound 375 D44 Compound 376 D45 Compound 377 D46 Compound 378 D47 Compound 379 D48 Compound 380 D49 Compound 381 D50 Compound 382 D51 Compound 383 D52 Compound 384 D53 Compound 385 D54 Compound 386

One embodiment of invertebrate pest control agents (e.g., insecticides and acaricides) for mixing with compounds of Formula 1 (and N-oxides and salts thereof) include sodium channel modulators such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibitors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and triazamate; neonicotinoids such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal macrocyclic lactones such as spinetoram, spinosad, abamectin, avermectin and emamectin; GABA (γ-aminobutyric acid)-regulated chloride channel blockers such as endosulfan, ethiprole and fipronil; chitin synthesis inhibitors such as buprofezin, cyromazine, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron and triflumuron; juvenile hormone mimics such as diofenolan, fenoxycarb, methoprene and pyriproxyfen; octopamine receptor ligands such as amitraz; ecdysone agonists such as azadirachtin, methoxyfenozide and tebufenozide; ryanodine receptor ligands such as ryanodine, anthranilic diamides such as chlorantraniliprole, cyantraniliprole and flubendiamide; nereistoxin analogs such as cartap; mitochondrial electron transport inhibitors such as chlorfenapyr, hydramethylnon and pyridaben; lipid biosynthesis inhibitors such as spirodiclofen and spiromesifen; cyclodiene insecticides such as dieldrin; cyflumetofen; fenothiocarb; flonicamid; metaflumizone; pyrafluprole; pyridalyl; pyriprole; pymetrozine; spirotetramat; and thiosultap-sodium. One embodiment of biological agents for mixing with compounds of component (a) include nucleopolyhedro virus such as HzNPV and AfNPV; Bacillus thuringiensis and encapsulated delta-endotoxins of Bacillus thuringiensis such as Cellcap, MPV and MPVII; as well as naturally occurring and genetically modified viral insecticides including members of the family Baculoviridae as well as entomophagous fungi. Of note is a composition comprising component (a) and at least one additional biologically active compound or agent selected from the Invertebrate Pest Control Agents listed in Table D1 above.

The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Table A for compound descriptions. The following abbreviations are used in the Index Tables which follow: Me is methyl, Ph is phenyl, OMe is methoxy, —CN is cyano, —NO₂ is nitro. Also, “pyridin-2-yl” is synonymous with “2-pyridinyl”, “pyridin-3-yl” is synonymous with “3-pyridinyl”, and “pyrimidin-5-yl” is synonymous with 5-pyrimidinyl”. The abbreviation “Ex.” stands for “Example” and is followed by a number indicating in which example the compound is prepared. “Cmpd No.” means compound number. Mass spectra (M.S.) are reported as the molecular weight of the highest isotopic abundance parent ion (M+1) formed by addition of H⁺ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP⁺).

INDEX TABLE A

Cmpd No. R¹ R² Q¹ Q² X M.S 1 (Ex. 1) H Me 2,4-di-F—Ph 3-Cl—Ph NH ** 2 H Me 2,4-di-F—Ph 3,5-di-OMe—Ph NH 360 3 H Me 2,4-di-F—Ph 3-Cl—Ph NMe * 4 H Me 4-Cl—Ph 2,4-di-F—Ph NH 334 5 H Me 4-Cl—Ph 3,5-di-F—Ph NH 334 6 H Me 4-Cl—Ph 3,5-di-F—Ph NMe 348 7 H Me 2-Cl-4-F—Ph 3-Cl-4-F—Ph NH 369 8 H Me 2-Cl-4-F—Ph 3-F—Ph NH 334 9 H Me 2-Cl-4-F—Ph 3,5-di-F—Ph NH 352 10 H Me 4-Cl—Ph 2,3,5-tri-F—Ph NH 352 11 H Me 2-Cl-4-F—Ph 4-F—Ph NH 334 12 H Me 2-Cl-4-F—Ph 2-F—Ph NH 334 13 H Me 2-Cl-4-F—Ph 2,4-di-F—Ph NH 352 14 H Me 2,4,6-tri-F—Ph 3-F-4-Cl—Ph NH 370 15 H Me 2-F-4-OMe—Ph 4-Cl—Ph O 347 16 H Me 3,5-di-OMe—Ph 4-Cl—Ph O 359 17 (Ex. 2) H Me 2-Cl-4-F—Ph 2,6-di-F-4-OMe—Ph NH ** 18 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph NH 370 19 H Me 2-Cl-4-F—Ph 4-Cl—Ph NH 350 20 H Me 2-Cl-4-F—Ph 2-F-4-NO₂—Ph O 380 21 H Me 2-Cl-4-F—Ph 2-F-4-OMe—Ph O 365 22 H Me 2,6-di-F-4-OMe—Ph 4-Cl—Ph NH 364 23 H Me 2,6-di-F-4-OMe—Ph 2,4-di-F—Ph NH 366 24 (Ex. 3) H Me 2,6-di-F-4-OMe—Ph 2,4,6-tri-F—Ph NH ** 25 H Me 3-Cl—Ph 2,6-di-F-4-OMe—Ph NH 364 26 H Me 2,4,6-tri-F—Ph 4-NO₂—Ph O 364 27 H Me 2,4,6-tri-F—Ph 4-Cl—Ph O 353 28 H Me 4-Cl—Ph 2,4,6-tri-F—Ph NH 352 29 H Me 4-Cl—Ph 2,6-di-F-4-OMe—Ph NH 364 30 H Me 2,4,6-tri-F—Ph 2,6-di-Cl-4-CF₃—Ph O 455 31 H Me 2,4,6-tri-F—Ph 2,6-di-F-4-CN—Ph O 380 32 H Me 2,4,6-tri-F—Ph 2-Cl-4-NO₂—Ph O 398 33 H Me 4-Cl—Ph 2,6-di-F—Ph NH 334 34 H Me 2,6-di-F-4-OMe—Ph 6-Cl-pyridin-3-yl NH 365 35 H Me 3,4-di-F—Ph 2,4,6-tri-F—Ph NH 354 36 H Me 3,4-di-F—Ph 2,6-di-F-4-OMe—Ph NH 366 37 H Me 2,6-di-F—Ph 3,5-di-OMe—Ph NH 360 38 H Me 2,4,6-tri-F—Ph 2,4-di-Cl—Ph O 387 39 H Me 2,4,6-tri-F—Ph 5-Cl-pyridin-2-yl O 354 40 H Me 2,6-di-F-4-OMe—Ph 2,4-di-Cl—Ph O 399 41 H Me 2,4-di-F—Ph 2,4,6-tri-F—Ph NH 354 42 H Me 2,4-di-F—Ph 2,6-di-F-4-OMe—Ph NH 366 43 H Me 3-F—Ph 2,6-di-F-4-CN—Ph O 344 44 H Me 4-Cl—Ph 2,6-di-F-4-CN—Ph O 360 45 (Ex. 4) H Me 2-Cl-4-F—Ph 2,6-di-F-4-CN—Ph O ** 46 H Me 2-F-4-OMe—Ph 2,6-di-F-4-CN—Ph O 374 47 H Me 2,6-di-F-4-OMe—Ph 5-Cl-pyridin-2-yl O 366 48 H Me 2,6-di-F-4-OMe—Ph 3,4-di-F—Ph NH 366 49 H Me 2,6-di-F-4-OMe—Ph 3-F-4-Cl—Ph NH 382 50 H Me 2,6-di-F-4-OMe—Ph 4-Me—Ph NH 344 51 H Me 2,6-di-F-4-OMe—Ph 2,4-di-OMe—Ph NH 390 52 H Me 4-Me—Ph 2-Cl-4-NO₂—Ph O 358 53 Ph Me 2,4,6-tri-F—Ph 2,6-di-F-4-NO₂—Ph O 476 54 (Ex. 8) H Me 2,4,6-tri-F—Ph 2,6-di-F-4-NO₂—Ph O ** 55 H Me 4-Me—Ph 2-Cl-4-OMe—Ph O 343 56 H Me 4-Cl—Ph 4-OMe—Ph NH 328 57 H Me 2,4-di-Cl—Ph 2,4-di-OMe—Ph NH 392 58 (Ex. 10) H Me 2,6-di-F-4-OMe—Ph 2,6-di-F-4-Cl—Ph O ** 59 H Me 2,6-di-F-4-OMe—Ph 2,4-di-OMe-6-Cl—Ph NH 424 60 H Me 4-Cl—Ph 2-Cl-4-OMe—Ph NH 362 61 Me Me 4-Cl—Ph 2,6-di-F—Ph NH 348 62 H Me 2,4-di-Cl—Ph 2,6-di-F-4-OMe—Ph NH 398 63 Me Me 2,6-di-F—Ph 3,5-di-OMe—Ph NH 374 64 H Me 2,4,6-tri-F—Ph 3,5-di-Cl-pyridin-2-yl O 388 65 —CO₂Et Me 2,4,6-tri-F—Ph 2,6-di-F, 4-NO₂—Ph O 472 66 H Me 2,6-di-F-4-OMe—Ph 5-Me-pyridin-2-yl NH 345 67 H Me 2-Cl-4-F—Ph 5-CN-pyridin-2-yl NH 342 68 —CO₂H Me 2,4,6-tri-F—Ph 2,6-di-F-4-NO₂—Ph O 444 69 (Ex. 5) H Me 2,4-di-Cl—Ph 2,4-di-F—Ph NH ** 70 Me Me 2,4-di-Cl—Ph 2,4-di-F—Ph NH 382 71 H Me 2-Cl-4-F—Ph 2-F-4-(NHC(O)Me)—Ph O 392 72 H Me 2,4-di-F—Ph 3,4-di-OMe—Ph NH 360 73 H Me 2-Cl-4-F—Ph 3,5-di-Cl-pyridin-2-yl NH 387 74 H Me 2,4-di-Cl—Ph 3,4-di-OMe—Ph NH 392 75 H Me 2,4-di-Cl—Ph 2,4,6-tri-F—Ph NH 386 76 H Me 2,4-di-F—Ph 6-Cl-pyridin-3-yl NH 331 77 H Me 2,6-di-F-4-OMe—Ph 2,6-di-F-4-NH₂—Ph O 382 78 H Me 2,4,6-tri-F—Ph 2,6-di-F-4-OMe—Ph NH 384 79 H Me 4-Me—Ph 2,4,6-tri-F—Ph NH 332 80 H Me 4-Me—Ph 2,6-di-F-4-OMe—Ph NH 344 81 H Me 2,6-di-F-4-OMe—Ph 5-Cl-2,4-di-OMe—Ph NH 424 82 H Me 2,6-di-F-4-OMe—Ph 2,6-di-F-4-CN—Ph NH 391 83 H Me 2,6-di-F-4-OMe—Ph 2,6-di-F-4-OMe—Ph NH 396 84 H Me 2,6-di-F-4-OMe—Ph 2,6-di-F—Ph O 367 85 H Me 3,5-di-OMe—Ph 2,6-di-F-4-CN—Ph O 386 86 H Me 6-Cl-pyridin-3-yl 2,6-di-F-4-CN—Ph O 361 87 H Me 2,6-di-F-4-OMe—Ph 2-Cl-4-F—Ph NH 382 88 H Me 2,6-di-F-4-OMe—Ph 4-F-2-Me—Ph NH 362 89 H Me 4-F-2-OMe—Ph 2,6-di-F-4-CN—Ph O 374 90 H Me 2,6-di-F-4-OMe—Ph 4-Br-2,6-di-F—Ph O 447 91 H Me 2-Cl-4-F—Ph 2,6-di-F-4-CN—Ph NH 377 92 H Me 2,4,6-tri-F—Ph 2,6-di-F-4-CN—Ph NH 379 93 H Me 2,4,6-tri-F—Ph 3,4-di-OMe—Ph NH 378 94 H Me 2,4,6-tri-F—Ph 6-OMe-pyridin-3-yl NH 349 95 H Me 2,6-di-F-4-OMe—Ph 6-OMe-pyridin-3-yl NH 361 96 H Me 2,4,6-tri-F—Ph 2-F-4-CN—Ph O 362 97 H Me 4-F-2-Me—Ph 2,6-di-F-4-CN—Ph O 358 98 H Me 2,4,6-tri-F—Ph 2-Cl-4-CN—Ph O 378 99 H Me 2,4,6-tri-F—Ph 2,5-di-F-4-CN—Ph O 380 100 H Me 2,4,6-tri-F—Ph 5-Cl-2,4-di-OMe—Ph NH 412 101 H Me 2,4,6-tri-F—Ph 3,5-di-Cl-pyridin-2-yl NH 386 102 H Me 2,6-di-F-4-OMe—Ph 3,5-di-Cl-pyridin-2-yl NH 398 103 H Me 2,6-di-F-4-OH—Ph 2,4-di-F—Ph NH 352 104 H Me 2-Cl-4-OMe—Ph 2,4,6-tri-F—Ph NH 382 105 H Me 2,6-di-F-4-OS(O)₂CF₃ 2,4-di-F—Ph NH 484 106 H Me 2,6-di-F-4-CN—Ph 2,4-di-F—Ph NH 361 107 H Me 2-Cl-4-F—Ph 2,6-di-Cl-pyridin-3-yl NH 386 108 H c-Pr 2-Cl-4-F—Ph 2,4-di-F—Ph NH 378 109 H Me 2,4,6-tri-F—Ph 3,5-di-F-pyridin-2-yl NH 355 110 H Me 2,6-di-F-4-CN—Ph 4-Cl—Ph NH *** 111 H Me 2,6-di-F-4-CN—Ph 4-F—Ph NH *** 112 H Me 2,6-di-F-4-CN—Ph 2-Cl-4-F—Ph NH *** 113 H Me 2,6-di-F-4-CN—Ph 3-F-4-OMe—Ph NH *** 114 H Me 2,6-di-F-4-CN—Ph 3,4-di-F—Ph NH *** 115 H Me 2,6-di-F-4-CN—Ph 3-Cl—Ph NH *** 116 H Me 2-Cl-4-F—Ph 3-F-5-CN—Ph O 360 117 H Me 2,6-di-F-4-OMe—Ph 2-Cl-4-CN—Ph NH 389 118 H Me 2-Cl-4-F—Ph 2-F-4-CN—Ph O 360 119 H Me 2-Cl-4-F—Ph 2-Cl-4-NO₂—Ph O 396 120 H Me 2,4,6-tri-F—Ph 2-F-4-CN—Ph NH 361 121 H Me 2-Cl-4-F—Ph 2,6-di-F-4-NO₂—Ph O 398 122 H Me 2-Cl-4-F—Ph 4-F-2-NO₂—Ph O 380 123 H Me 2,6-di-F-4-CN—Ph 3,4-di-Cl—Ph NH *** 124 H Me 2,6-di-F-4-CN—Ph 4-Me—Ph NH *** 125 H Me 2,6-di-F-4-CN—Ph 4-Cl-3-F—Ph NH *** 126 H Me 2,6-di-F-4-CN—Ph 4-OMe—Ph NH *** 127 H Me 2,6-di-F-4-CN—Ph 4-F-3-OMe—Ph NH 373 128 H Me 2,6-di-F-4-OMe—Ph 3,5-di-F-pyridin-2-yl NH 367 129 H Me 2,4,6-tri-F—Ph 4-Cl-3-F—Ph O *** 130 H Me 2,4,6-tri-F—Ph 4-Br-3-F—Ph O *** 131 H Me 2,4,6-tri-F—Ph 3-F-4-NO₂—Ph O *** 132 H Me 2-Cl-4-F—Ph 3,4,5-tri-F—Ph NH 370 133 H Me 2,6-di-F-4-CN—Ph 2,4,6-tri-F—Ph NH *** 134 H Me 2,6-di-F-4-CN—Ph 2,6-di-F-4-OMe—Ph NH *** 135 H Me 2,4,6-tri-F—Ph 3-Me-4-NO₂—Ph O *** 136 H Me 2,6-di-F-4-CN—Ph 3-F—Ph NH *** 137 H Me 2,6-di-F-4-CN—Ph 2,5-di-F—Ph NH *** 138 H Me 2,6-di-F-4-CN—Ph 2,4,5-tri-F—Ph NH *** 139 H Me 2-Cl-4-F—Ph 2-Cl-4-CN—Ph O 376 140 H Me 2,6-di-F-4-OMe—Ph 2,6-di-F-4-CN—Ph O 392 141 H Me 2,6-di-F-4-OEt—Ph 2,4-di-F—Ph NH 380 142 H Me 2,6-di-F-4-CN—Ph 5-Cl-2-F—Ph NH *** 143 H Me 2,6-di-F-4-CN—Ph 4-Cl-2-F—Ph NH *** 144 H Me 2,6-di-F-4-CN—Ph 3-Cl-4-F—Ph NH *** 145 H Me 2,6-di-F-4-CN—Ph 2,3-di-F—Ph NH *** 146 H Me 2,6-di-F-4-CN—Ph 2,5-di-Cl—Ph NH *** 147 H Me 2,6-di-F-4-CN—Ph 2,3-di-Cl—Ph NH *** 148 H Me 2-Cl-4-F—Ph 2,5-di-F-4-CN—Ph O 378 149 H Me 2-Cl-4-F—Ph 4-F-2-CN—Ph O 360 150 H Me 2-Cl-4-F—Ph 2-Cl-4,5-di-CN—Ph O 401 151 H Me 2,4,6-tri-F—Ph 3-OMe-4-NO₂—Ph O *** 152 H Me 2,6-di-F-4-OMe—Ph 4-Cl-3-F—Ph O 383 153 H Me 2,6-di-F-4-OMe—Ph 4-Br-3-F—Ph O 429 154 H Me 2-Cl-4-F—Ph 3,5-di-F-pyridin-2-yl NH 353 155 H Me 2-Cl-4-OMe—Ph 2,6-di-F-4-CN—Ph O 390 156 H Me 2,4,6-tri-F—Ph 3-CN-4-NO₂—Ph O *** 157 H Me 2,4,6-tri-F—Ph 4-Cl-3-Me—Ph O *** 158 H Me 2-Cl-4-F—Ph 2,6-di-F-4-OMe—Ph NEt 410 159 H Me 2-Cl-4-F—Ph 2,6-di-F-4-OMe—Ph NCH₂CH═CH₂ 422 160 H Me 2-Cl-4-OMe—Ph 2,4-di-F—Ph NH 364 161 H Me 2-Cl-4-OMe—Ph 2,6-di-F—Ph NH 364 162 H Me 2-Cl-4-F—Ph 2-Cl-4-CN—Ph NH 375 163 H Me 2,4,6-tri-F—Ph 2-Cl-4,5-di-CN—Ph O 403 164 H Me 2,4,6-tri-F—Ph 4-Cl-3-OMe—Ph O *** 165 H Me 2,4,6-tri-F—Ph 4-Br-3-Me—Ph O *** 166 H Me 2,4,6-tri-F—Ph 4-Br-3-OMe—Ph O 429 167 H Me 2,4,6-tri-F—Ph 2,3,5-tri-F—Ph O 373 168 H Me 2-Cl-4-F—Ph 3,4-di-CN—Ph O 367 169 H Me 2,4,6-tri-F—Ph 3,4-di-CN—Ph O 369 170 H Me 2,4-di-F—Ph 2,6-di-F-4-CN—Ph O 362 171 H Me 2-Cl-4-F—Ph 2,3,6-tri-F—Ph NH 370 172 H Me 2-Cl-4-F—Ph 2,6-di-F—Ph NH 352 173 H Me 2-Cl-4-F—Ph 2,5-di-F—Ph NH 352 174 H Me 2-Cl-4-OMe—Ph 2,3,6-tri-F—Ph NH 382 175 H Me 2-Cl-4-F—Ph 2-Cl-4-F—Ph NH 368 176 H Me 2-Cl-4-OMe—Ph 2,5-di-F—Ph NH 364 177 H Me 2-Cl-6-F—Ph 2,4-di-F—Ph NH 352 178 H Me 2,6-di-F—Ph 2,4-di-F—Ph NH *** 179 H Me 2,6-di-F—Ph 2,4-di-Cl—Ph NH *** 180 H Me 2,6-di-F—Ph 2-F-4-OMe—Ph NH *** 181 H Me 2-F—Ph 2,4-di-F—Ph NH 318 182 H Me 2-F—Ph 2,4,6-tri-F—Ph NH 336 183 H Me 2-F—Ph 2,6-di-F-4-OMe—Ph NH 348 184 H Me 2-F—Ph 4-F—Ph NH 300 185 H Me 2,6-di-F-4-OMe—Ph 4-Cl-3-Me—Ph O 379 186 H Me 2,6-di-F-4-OMe—Ph 4-Br-3-Me—Ph O *** 187 H Me 2,4,6-tri-F—Ph 3-F-4-Me—Ph O *** 188 H Me 2,6-di-F-4-OMe—Ph 3-F-4-Me_Ph O 363 189 H Me 2-Cl-4-F—Ph 3,5-di-F-pyridin-2-yl O 354 190 H Me 2-Cl-6-F—Ph 2,6-di-F-4-OMe—Ph NH 382 191 H Me 2-Cl-6-F—Ph 2,4,6-tri-F—Ph NH 369 192 H Me 2-Cl-6-F—Ph 2,6-di-F-4-CN—Ph NH 377 193 H Me 2-Cl-6-F—Ph 2-Cl-4-F—Ph NH 368 194 H Me 2,4-di-F—Ph 4-F—Ph NH *** 195 H Me 2,4-di-F—Ph 4-Cl—Ph NH *** 196 H Me 2,6-di-F—Ph 2-F-4-CN—Ph NH 343 197 H Me 2,6-di-F—Ph 2,5-di-F—Ph NH *** 198 H Me 2,6-di-F—Ph 2,3-di-F—Ph NH *** 199 H Me 2,6-di-F—Ph 4-F-2-OMe—Ph NH *** 200 H Me 2,6-di-F—Ph 3-OMe—Ph NH *** 201 H Me 2,6-di-F—Ph 2-Cl-4-OMe—Ph NH *** 202 H Me 2,3-di-F—Ph 2,4-di-F—Ph NH 336 203 H Me 2,3-di-F—Ph 2,4,6-tri-F—Ph NH 354 204 H Me 2,3-di-F—Ph 2,6-di-F-4-OMe—Ph NH 366 205 H Me 2,3-di-F—Ph 4-F—Ph NH 318 206 H Me 2,6-di-F-4-OMe—Ph 4-Cl—Ph O 365 207 H Me 2,4-di-F—Ph 2-Cl-4-F—Ph NH *** 208 H Me 2,6-di-F-4-OMe—Ph 2,4-di-F—Ph CHOH 381 209 H Me 2,4,6-tri-F—Ph 3,4-di-Me—Ph O *** 210 H Me 2,6-di-F-4-OMe—Ph 3,4-di-Me—Ph O *** 211 H Me 2,6-di-F-4-OMe—Ph 4-Cl-3-OMe—Ph O *** 212 H Me 2,6-di-F-4-OMe—Ph 4-Br-3-OMe—Ph O *** 213 H Me 2,4,6-tri-F—Ph 3-OMe—Ph O 349 214 H Me 2,4-di-F—Ph 2,3-di-F—Ph NH *** 215 H Me 2,6-di-F—Ph 2-Cl-5-OMe—Ph NH *** 216 H Me 2,6-di-F—Ph 2-F-5-OMe—Ph NH *** 217 H Me 2,4,6-tri-F—Ph 3-OMe-4-Me—Ph O *** 218 H Me 2,6-di-F-4-OMe—Ph 4-Cl-3-CN—Ph O *** 219 H Me 2,4,6-tri-F—Ph 3-Me—Ph O 333 220 H Me 2,6-di-F-4-OMe—Ph 3-Me—Ph O 345 221 H Me 2,6-di-F-4-OMe—Ph 3-OMe—Ph O 361 222 H Me 2,4,6-tri-F—Ph 3-CN—Ph O 344 223 H Me 2,6-di-F-4-OMe—Ph 3-CN—Ph O 356 224 H Me 2,4,6-tri-F—Ph 4-Cl-3-CN—Ph O *** 225 H Me 2,4,6-tri-F—Ph 4-Br-3-CN—Ph O *** 226 H Me 2,4-di-F—Ph 2,5-di-F—Ph NH *** 227 H Me 2,4-di-F—Ph 2-Cl-5-OMe—Ph NH *** 228 H Me 2,4-di-F—Ph 2-F-4-OMe—Ph NH *** 229 H Me 2,4-di-F—Ph 2,4,5-tri-F—Ph NH *** 230 H Me 2,4-di-F—Ph 2,4-di-F—Ph NH 336 231 H Me 2,4-di-F—Ph 2,3-di-Cl—Ph NH *** 232 H Me 2-Br-4-F—Ph 2,6-di-F-4-CN—Ph O 423 233 H Me 2-Br-4-F—Ph 2,5-di-F-4-CN—Ph O 423 234 H Me 2-Cl-4-F—Ph 4-F-3-CN—Ph NH 359 235 H Me 2-Cl-4-F—Ph 2-Cl-5-CN—Ph NH 375 236 H Me 2-CF₃—Ph 2-Cl-4-F—Ph NH 384 237 H Me 2-CF₃—Ph 4-F—Ph NH 350 238 H Me 2-CF₃—Ph 2,4-di-F—Ph NH 368 239 H Me 2-CF₃—Ph 2,4,6-tri-F—Ph NH 386 240 H Me 2-CF₃—Ph 2,6-di-F-4-OMe—Ph NH 398 241 H Me 2,4,6-tri-F—Ph 3-Cl-pyridin-2-yl NH 353 242 H Me 2,4-di-F—Ph 2-Cl-4-OMe—Ph NH *** 243 H Me 2,4-di-F—Ph 2,4-di-Cl—Ph NH *** 244 H Me 2,4-di-F—Ph 2-F-5-OMe—Ph NH *** 245 H Me 2,4-di-F—Ph 2,5-di-Cl—Ph NH *** 246 H Me 2,4-di-F—Ph 2-F-4-CN—Ph NH *** 247 H Me 2,6-di-F—Ph 2,6-di-F—Ph NH *** 248 H Me 2-Br—Ph 2,4,6-tri-F—Ph NH 398 249 H Me 2,6-di-F-4-OMe—Ph 3-OMe-4-Me—Ph O *** 250 H Me 2,4,6-tri-F—Ph 3-CN-4-Me—Ph O *** 251 H Me 2-CF₃—Ph 3,5-di-Cl-pyridin-2-yl NH 401 252 H Me 2-Cl-6-F—Ph 3,5-di-Cl-pyridin-2-yl NH 387 253 H Me 2-F-6-CF₃—Ph 2-Cl-4-F—Ph NH 402 254 H Me 2-F-6-CF₃—Ph 4-F—Ph NH 368 255 H Me 2-F-6-CF₃—Ph 2,4-di-F—Ph NH 368 256 H Me 2,4-di-F—Ph 2,6-di-F—Ph NH *** 257 H Me 2,6-di-F—Ph 2,6-di-F-4-OMe—Ph NH *** 258 H Me 2,6-di-F-4-OMe—Ph 4-Br-3-CN—Ph O *** 259 H Me 2,6-di-F-4-OMe—Ph 3-CN-4-Me—Ph O *** 260 H Me 2-Br-4-F—Ph 3-F-5-CF₃-pyridin-2-yl O 449 261 H Me 2-Br-4-F—Ph 3-Cl-5-CF₃-pyridin-2-yl O 465 262 H Me 2-F-6-CF₃—Ph 2,4,6-tri-F—Ph NH 404 263 H Me 2-F-6-CF₃—Ph 2,6-di-F-4-OMe—Ph NH 416 264 H Me 2-F-6-CF₃—Ph 3,5-di-F-pyridin-2-yl NH 387 265 H Me 2-Cl-4-F—Ph 2-Br-4-F—Ph NH 413 266 H Me 2-Br-4-F—Ph 2,4,6-tri-F—Ph NH 415 267 H Me 2-Cl-4-OMe—Ph 3,5-di-Cl-pyridin-2-yl NH 399 268 H Me 2-Cl-4-F—Ph 2-Cl-pyrimidin-5-yl NH *** 269 H Me 2-Cl-4-F—Ph 2-Me-pyrimidin-5-yl NH *** 270 H Me 2-Cl-4-F—Ph pyrimidin-5-yl NH *** 271 H Me 2-Cl—Ph 2,6-di-F-4-CN—Ph O *** 272 H Me 2-Br—Ph 2,6-di-F-4-CN—Ph O *** 273 H Me 2,3-di-Cl—Ph 2,6-di-F-4-CN—Ph O *** 274 H Me 2,3-di-F—Ph 2,6-di-F-4-CN—Ph O *** 275 H Me 2,5-di-Cl—Ph 2,6-di-F-4-CN—Ph O *** 276 H Me 2-Cl-5-F—Ph 2,6-di-F-4-CN—Ph O *** 277 H Me 2-Cl-5-OMe—Ph 2,6-di-F-4-CN—Ph O *** 278 H Me 2-F-5-OMe—Ph 2,6-di-F-4-CN—Ph O *** 279 H Me 2-Cl-6-F—Ph 3,5-di-F-pyridin-2-yl NH 353 280 H Me 2-CF₃—Ph 3,5-di-F-pyridin-2-yl NH 369 281 H Me 2,4-di-F—Ph 2-Cl-3-OMe—Ph NH *** 282 H Me 2-Cl-4-OMe—Ph 2,4-di-Cl—Ph NH 397 283 H Me 2-Cl-6-F—Ph 2,4-di-Cl—Ph NH 386 284 H Me 2-Br-4-F—Ph 2-F-4-CN—Ph O 406 285 H Me 2-Br-4-F—Ph 2-Cl-4-CN—Ph O 422 286 H Me 2-Cl-4-F—Ph 4-Cl-2,6-di-F—Ph NH 386 287 H Me 2-Cl-4-F—Ph 2-Cl-4,6-di-F—Ph NH 386 288 H Me 2-Cl-4-F—Ph 4-OMe—Ph NH 346 289 H Me 2,6-di-F—Ph 2-Cl-3-OMe—Ph NH *** 290 H Me 2,4-di-F—Ph 2,6-di-F-4-CN—Ph NH *** 291 H Me 2,4-di-F—Ph 2-Cl-5-CN—Ph NH *** 292 H Me 2-Br-4-F—Ph 2-Cl-4,6-di-F—Ph NH 431 293 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph NMe *** 294 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph NEt *** 295 H Me 2-Br-4-F—Ph 3,5-di-Cl-pyridin-2-yl NH 430 296 H Me 2-Cl-4-F—Ph 2,6-di-Cl-4-OMe—Ph NH 413 297 H Me 2,6-di-F—Ph 2-Cl-4,6-di-F—Ph NH 370 298 H Me 2-Cl-6-F—Ph 2-Cl-4,6-di-F—Ph NH 386 299 H Me 2-Cl-4-F—Ph 2,4-di-Cl—Ph NH 383 300 H Me 2,6-di-F—Ph 2,4,6-tri-F—Ph NH *** 301 H Me 2,6-di-F—Ph 2,6-di-F-4-CN—Ph NH *** 302 H Me 2,3-di-Cl—Ph 2,4-di-F—Ph NH 368 303 H Me 2,3-di-Cl—Ph 3,5-di-Cl-pyridin-2-yl NH 400 304 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph NS(O)₂Me *** 305 H Me 2-F—Ph 2,6-di-F-4-CN—Ph O *** 306 H Me 2-CF₃—Ph 2,6-di-F-4-CN—Ph O *** 307 H Me 2-Cl-5-CF₃—Ph 2,6-di-F-4-CN—Ph O *** 308 H Me 2-Cl-pyridin-3-yl 2,6-di-F-4-CN—Ph O *** 309 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph NCH₂OMe *** 310 H Me 2-Cl-4-OMe—Ph 2-F-4-CN—Ph O 372 311 H Me 2-Cl-4-OMe—Ph 2-Cl-4-CN—Ph O 388 312 H Me 2-Br-4-F—Ph 2,4-di-F—Ph NH 398 313 H Me 2-Br-4-F—Ph 2-Br-4-F—Ph NH 458 314 H Me 2-Br-4-F—Ph 2-Cl-4-F—Ph NH 414 315 H Me 2-Cl—Ph 2,4-di-F—Ph NH 334 316 H Me 2-Br-4-F—Ph 2,6-di-Cl-4-F—Ph NH 448 317 H Me 2-Br-4-F—Ph 4-OMe—Ph NH 392 318 H Me 2-Br-4-OMe—Ph 2-Cl-4-CN—Ph O 433 319 H Me 2-Br-4-OMe—Ph 2-F-4-CN—Ph O 418 320 H Me 2-Cl—Ph 3,5-di-Cl-pyridin-2-yl NH 368 321 H Me 2,6-di-F—Ph 3,5-di-Cl-pyridin-2-yl NH 369 322 H Me 2-Cl-4-F—Ph 2-Cl-4-OMe—Ph NH 380 323 H Me 2-Br-4-F—Ph 2,6-di-Cl-4-OMe—Ph NH 459 324 H Me 2-Br-4-F—Ph 2-Cl-4-OMe—Ph NH 425 325 H Me 2-Cl-4-F—Ph 2-Cl-4-OEt—Ph NH 394 326 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph NCH₂CN 409 327 H Me 2,6-di-Cl—Ph 2,4-di-Cl—Ph NH *** 328 H Me 2,4-di-F—Ph 3,5-di-Cl-pyridin-2-yl NH 369 329 H Me 2,5-di-F—Ph 2,6-di-F-4-CN—Ph O *** 330 H Me 2-Cl-4,6-di-F—Ph 2,6-di-F-4-CN—Ph NH 395 331 H Me 2-Cl-4-CN—Ph 2,4-di-F—Ph NH 359 332 H Me 2-Cl-4-CN—Ph 2-Cl-4,6-di-F—Ph NH 393 333 H Me 2,6-di-Cl—Ph 4-OMe—Ph NH *** 334 H Me 2,6-di-Cl—Ph 2-Cl-4-F—Ph NH *** 335 H Me 2-Cl-4-CN—Ph 2,6-di-F—Ph NH 359 336 H Me 2-Cl-4-CN—Ph 4-Cl-2,6-di-F—Ph NH 393 337 H Me 2,6-di-Cl—Ph 4-F—Ph NH *** 338 H Me 2-Cl-4-CN—Ph 2-Cl-4-F—Ph NH 375 339 H Me 2,6-di-Cl—Ph 2,4-di-F—Ph NH *** 340 H Me 2,6-di-Cl—Ph 2-Br-4-F—Ph NH *** 341 H Me 2,6-di-Cl—Ph 2,6-di-Cl-4-F—Ph NH *** 342 H Me 2-Cl-6-F—Ph 2-F-4-CN—Ph O 360 343 H Me 2,4-di-F—Ph 2-Cl-4,6-di-F—Ph NH 369 344 H Me 2-Cl-4-F—Ph 2-F-4-NO₂—Ph NH 380 345 H Me 2-Cl-4-F—Ph 2-F-5-NO₂—Ph NH 380 346 H Me 2,4-di-F—Ph 2-Br-4-F—Ph NH 398 347 H Me 4-Cl-2-F—Ph 2-F-4-CN—Ph O 360 348 H Me 2,4-di-F—Ph 2-Br-6-Cl-4-F—Ph NH 432 349 H Me 2,6-di-F—Ph 4-Cl-2,6-di-F—Ph NH 370 350 H Me 2-Cl-4-F—Ph 4-F—Ph CHOH 349 351 (Ex. 6) H Me 2-Cl-4-F—Ph 2,4-di-F—Ph CHOH ** 352 H Me 2-Cl-4-F—Ph 2-Cl-4-F—Ph CHOH 383 353 H Me 2,4-di-Cl—Ph 2,6-di-F—Ph NH *** 354 H Me 2,4-di-Cl—Ph 2-Cl-4-F Ph NH *** 355 H Me 2,4-di-Cl—Ph 4-OMe—Ph NH *** 356 H Me 2-Cl-4-F—Ph 2,3,6-tri-F—Ph CHOH 385 357 H Me 2,4-di-F—Ph 4-Cl-2,6-di-F—Ph NH 370 358 H Me 2,6-di-F—Ph 2-Cl-4-CN—Ph O 360 359 H Me 2,4-di-F—Ph 2-F-4-CN—Ph O 376 360 H Me 2-Br-4-F—Ph 4-Cl-2,6-di-F—Ph NH 432 361 H Me 2,6-di-F—Ph 2-F-4-CN—Ph O 344 362 H Me 2,4-di-Cl—Ph 2-Cl-4-CN—Ph O 394 363 H Me 2,4-di-Cl—Ph 2,6-di-Cl-4-F—Ph NH *** 364 H Me 2,4-di-F—Ph 4-Br-2,6-di-F—Ph NH 416 365 H Me 2-Cl-4-F—Ph 4-Br-2,6-di-F—Ph NH 432 366 H Me 2-Cl-4-F—Ph 4-Br-2-F—Ph NH 414 367 H Me 2-Cl-4-F—Ph 2,4-di-Cl-6-F—Ph NH 402 368 H Me 2,4-di-F—Ph 2,6-di-Cl-4-F—Ph NH 369 H Me 2-Cl-4-F—Ph 2,6-di-Cl-4-F—Ph NH 370 (Ex. 7) H Me 2-Cl-4-F—Ph 2,4-di-F—Ph C(═O) ** 371 (Ex. 9) H Me 2,4,6-tri-F—Ph 2,6-di-F-4-NH₂—Ph O ** 372 H Me 2,4-di-F—Ph 2-Br-4-CN—Ph O 373 H Me 2,4-di-F—Ph 2-Cl-4-CN—Ph O 374 H Me 2,4-di-F—Ph 2,4-di-Cl-6-F—Ph NH 386 375 H Me 2,6-di-F—Ph 2,6-di-Cl-4-F—Ph NH 376 H Me 2,4-di-F—Ph 2-Br-4,6-di-F—Ph NH 416 377 H Me 2-Cl-4-F—Ph 2-Br-4,6-di-F—Ph NH 432 378 H Me 2,6-di-F—Ph 4-Br-2,6-di-F—Ph NH 379 H Me 2,6-di-F—Ph 2-Br-4,6-di-F—Ph NH 380 H Me 2-Cl-6-F—Ph 2-Br-4,6-di-F—Ph NH 381 H Me 2-Cl-4-F—Ph 2,6-di-F-4-Cl—Ph CHOH 402 382 H Me 2-F-4-CN—Ph 2-Cl-4,6-di-F—Ph NH 383 H Me 2-F-4-CN—Ph 2,6-di-F-4-Cl—Ph NH 384 H Me 2-Cl-4-F—Ph 2-Cl-4,6-di-F—Ph CHOH 385 H Me 2,4-di-F—Ph 2-Br-4-F—Ph CHOH 386 H Me 2-Cl-4-F—Ph 2-Br-4-F—Ph CHOH 387 H Me 2-Cl-4-OH—Ph 2,4-di-F—Ph NH 350 388 H Me 2-Cl-4-OCH₂CN—Ph 2,4-di-F—Ph NH 389 389 H Me 2,4-di-F—Ph 4-Br-4-F—Ph NH 396 390 H Me 2,4-di-F—Ph 4-Br-2,6-di-Cl—Ph NH 448 391 H Me 2,4-di-Cl—Ph 2-Cl-4,6-di-F—Ph NH *** 392 H Me 2,4-di-Cl—Ph 4-Cl-2,6-di-F—Ph NH *** 393 H Me 2-Cl-4-F—Ph 4-OEt NH 360 394 H Me 2-Cl-4-F—Ph 4-Cl-2-F O 369 395 H Me 2,4-di-F—Ph 2-F-4-CN—Ph O 344 396 H Me 2,4-di-F—Ph 4-Cl-2-F—Ph NH 352 397 H Me 2,4-di-F—Ph 2,4-di-Cl-6-F—Ph NH 386 398 H Me 2,6-di-F—Ph 4-Cl-2-F—Ph NH 352 399 H Me 2,6-di-F-4- 2-F-4-CN—Ph O 445 (OCH₂CH₂CH₂NMe₂)—Ph 400 H Me 4-Cl—Ph 2,6-di-F—Ph NH 334 401 H Me 2-Cl-4-F—Ph 4-Cl-2,5-di-F—Ph NH 386 402 H Me 2-Br-4-F—Ph 4-Br-2,6-di-F—Ph NH 474 403 H Me 2-Cl-4-F—Ph 4-Br-2,6-di-Cl—Ph NH 464 404 H Me 2-Cl-4-F—Ph 2-Cl-4,5-di-F—Ph NH 386 405 H Me 2,4-di-F—Ph 2,4,6-tri-Cl—Ph NH 404 406 H Me 2,4-di-F—Ph 2-Br-4,6-di-F—Ph NH 416 407 H Me 2,4-di-F—Ph 4-Br-2-Cl—Ph NH 414 408 H Me 2-Br-4-F—Ph 4-Br-2,6-di-Cl—Ph NH 508 409 H Me 2-Br-4-F—Ph 4-Br-2-F—Ph NH 458 410 H Me 2-Cl-4-F—Ph 2,4,6-tri-Cl—Ph NH 420 411 H Me 2-Cl-4-F—Ph 2-Br-4,6-di-F—Ph NH 432 412 H Me 2-Cl-4-F—Ph 4-Br-2-Cl—Ph NH 430 413 H Me 2-Br-4-F—Ph 4-Br-2-Cl—Ph NH 474 414 H Me 2-Br-4-F—Ph 2,4,6-tri-Cl—Ph NH 464 415 H Me 2,4-di-F—Ph 4-F-2-I—Ph NH 444 416 H Me 2,4-di-F—Ph 2,4,6-tri-Me—Ph NH 342 417 H Me 2-Cl-4-F—Ph 4-Cl-2,5-di-F—Ph NH 386 418 H Me 2-Cl-4-F—Ph 2-Cl-4,5-di-F—Ph NH 386 419 H Me 2-Cl-4-F—Ph 2,4-di-F—Ph CHOAc 409 420 H Me 2-Cl-4-F—Ph pyridin-2-yl CHOH 332 421 H Me 2-Cl-4-F—Ph 4-Cl-2-F—Ph CHOH 384 422 H Me 2-Cl-4-F—Ph 2,4,6-tri-F—Ph CHOH 385 423 H Me 2-Cl-4-F—Ph 2-F-4-CN—Ph CHOH 374 424 H Me 2,4-di-F—Ph 4-Cl-2-F-6-I—Ph NH 478 425 H Me 2-Cl-4- 2,4-di-F—Ph NH 421 (OCH₂CH₂CH₂NHMe)—Ph 426 H Me 2-Cl-4- 2,4-di-F—Ph NH 422 (OCH₂CH₂CH₂OMe)—Ph 427 H Et 2-Cl-4-F—Ph 2,4-di-F—Ph NH 366 428 H Et 2-Cl-4-F—Ph 2,4-di-F—Ph CHOH 382 *¹H NMR data found in Index Table B **AP⁺ data or ¹H NMR data found in the Synthesis Examples ***MP data found in Index Table C

INDEX TABLE B Cmpd No. ¹H NMR Data (CDCl₃ solution unless indicated otherwise)^(a) 3 δ 7.11 (m, 1H), 6.99 (m, 1H), 6.75-6.85 (m, 3H), 6.58 (m, 1H), 6.40 (m, 1H), 3.58 (s, 3H), 3.07 (s, 3H), 2.21 (s, 3H). ^(a1)H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet and (m)-multiplet.

INDEX TABLE C Cmpd No. Melting Point ^(b) 110  85-87 111 165-167 112  80-82 113 135-137 114 147-149 115 168-170 123 171-173 124 135-137 125 138-140 126 142-144 129 127-130 130 129-131 131 129-133 133 160-162 134 228-230 135 112-117 136 152-154 137 165-167 138 171-173 142 186-188 143  93-95 144 176-178 145 142-144 146 145-147 147  60-62 151 150-158 156 107-114 157  96-101 164 106-110 165 111-113 178 110-112 179 105-107 180 130-132 186  78-84 187 107-113 194 133-135 195  98-100 197 115-117 198 106-108 199 134-136 200 139-141 201 109-111 207  57-59 209  92-96 210  73-77 211 110-114 212 130-134 214 105-107 215  90-92 216 152-154 217  72-76 218 112-117 224 132-135 225 123-126 226 139-141 227  99-102 228 133-135 229 144-146 231 108-110 242  91-93 243  82-84 244  95-97 245  73-75 246 182-184 247 156-158 249  83-87 250 126-129 256 171-173 257 172-174 258 121-124 259 97-100 268 178-180 269  80-85 270 172-176 271 132-135 272 132-134 273 152-153 274 141-143 275 168-171 276 115-117 277 131-134 278 112-114 281  49-52 289 148-150 290 181-183 291 146-149 293 116-118 294 113-115 300 178-180 301 168-170 304 186-191 305 101-105 306 134-138 307 161-166 308 142-145 309 118-123 327 118-120 329  98-100 333 177-179 334 117-119 337 186-188 339 135-136 340 137-139 341 151-153 353 169-171 354 111-113 355  90-92 363 229-231 391 181-183 392 155-157 ^(b) Melting point data are ° C..

Biological Examples of the Invention

General protocol for preparing test suspensions for Tests A-J: the test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-J. Spraying a 200 ppm test suspension to the point of run-off on the test plants was the equivalent of a rate of 500 g/ha. Unless otherwise indicated, the rating values indicate a 200 ppm test suspension was used. (An asterisk “*” next to the rating value indicates a 40 ppm test suspension was used.)

Test A

Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20° C. for 24 h. After a short drying period, the test suspension was sprayed to the point of run-off on the grape seedlings and then moved to a growth chamber at 20° C. for 4 days, after which time the test units were placed back into a saturated atmosphere at 20° C. for 24 h. Upon removal, visual disease ratings were made.

Test B

The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Botrytis cinerea (the causal agent of tomato Botrytis) and incubated in saturated atmosphere at 20° C. for 48 h, and then moved to a growth chamber at 24° C. for 3 additional days, after which time visual disease ratings were made.

Test C

The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Alternaria solani (the causal agent of tomato early blight) and incubated in a saturated atmosphere at 27° C. for 48 h, and then moved to a growth chamber at 20° C. for 5 days, after which time visual disease ratings were made.

Test D

The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 5 days, after which time visual disease ratings were made.

Test E

The test suspension was sprayed to the point of run-off on creeping bent grass (Agrostis sp.) seedlings. The following day the seedlings were inoculated with a bran and mycelial slurry of Rhizoctonia solani (the causal agent of turf brown patch) and incubated in a saturated atmosphere at 27° C. for 48 h, and then moved to a growth chamber at 27° C. for 3 days, after which time disease ratings were made.

Test F

The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria nodorum (the causal agent of Septoria glume blotch) and incubated in a saturated atmosphere at 24° C. for 48 h, and then moved to a growth chamber at 20° C. for 6 days, after which time visual disease ratings were made.

Test G

The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Septoria tritici (the causal agent of wheat leaf blotch) and incubated in saturated atmosphere at 24° C. for 48 h. and then the seedlings were moved to a growth chamber at 20° C. for 19 additional days, after which time visual disease ratings were made.

Test H

Wheat seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 2 days. At the end of this time the test suspension was sprayed to the point of run-off, and then the seedlings were moved to a growth chamber at 20° C. for 6 days after which time visual disease ratings were made.

Test I

The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita f. sp. tritici (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20° C. for 24 h, and then moved to a growth chamber at 20° C. for 7 days, after which time visual disease ratings were made

Test J

The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore dust of Erysiphe graminis f sp. tritici, (the causal agent of wheat powdery mildew) and incubated in a growth chamber at 20° C. for 8 days, after which time visual disease ratings were made.

Results for Tests A-J are given in Table A. In the Table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control (relative to the controls). A dash (-) indicates no test results.

TABLE A Cmpd No. Test A Test B Test C Test D Test E Test F Test G Test H Test I Test J 1 0 99 0 0 47 0 99 — 0 98 2 8 1 0 0 0 0 0 — 0 0 3 6 0 25 9 0 0 13 — 0 99 4 29 87 46 0 0 0 98 — 53 97 5 36 0 25 0 0 0 0 — 0 0 6 65 10 23 0 0 0 0 — 0 93 7 29 99 0 0 63 0 100 — 74 92 8 55 99 54 0 99 0 100 — 97 99 9 — 99 0 0 55 0 100 — 98 97 10 — 47 0 0 0 0 0 — 0 0 11 — 99 99 0 99 0 100 — 99 100 12 — 99 93 0 99 0 100 — 99 100 13 — 99 100 0 98 64 100 — 100 99 14 — 98 0 — — 0 99 — 99 98 15 — 99 67 — — 73 99 — 98 99 16 — 60 0 — — 0 47 48 28 0 17 — 100 100 — — 93 97 96 100 100 18 — 99 100 — — 99 95 99 100 100 19 — 100 85 — — 0 96 0 92 98 20 — 100 99 — — 100 100 79 100 99 21 — 98 100 — — 97 — — 100 99 22 — 90 85 — — 90 94 9 94 100 23 — 98 100 — — 99 93 92 100 100 24 — 98 100 — — 0 94 9 97 100 25 — 100 0 — — 0 100 0 94 79 26 — 99 83 — — 0 100 0 99 100 27 — 99 88 — — 0 95 0 25 87 28 — 99 0 — — 0 96 7 91 0 29 — 94 0 — — 0 98 0 46 0 30 — 7 0 — — 0 41 0 79 0 31 —  99* 98* — —  0* 47*  15*  79*  60* 32 — 99 0 — — 0 96 0 99 97 33 — 0 0 — — 0 95 0 18 0 34 — 100* 97* — —  0* 96*  0*  76*  0* 35 — 100 0 — — 0 95 0 97 100 36 — 100 0 — — 0 96 0 96 98 37 0 0 0 0 0 0 3 — 0 0 38 — 99 9 — — 0 97 0 99 99 39 — 100 99 — — 0 99 99 99 99 40 — 99 0 — — 0 94 92 99 99 41 — 100 99 — — 90 94 0 100 99 42 — 100 0 — — 0 93 0 94 82 43 — 76 0 — — 0 97 66 82 99 44 — 82 0 — — 0 96 7 9 0 45 — 100 100 — — 100 100 7 100 100 46 — 99 100 — — 99 100 37 100 99 47 — 100* 87* — —  0* 99*  37*  96*  99* 48 — 100 78 — — 0 99 0 98 98 49 — 100 17 — — 35 99 0 89 79 50 — 99 57 — — 0 100 0 98 99 51 — 100 0 — — 0 100 0 89 78 52 — 54 0 — — 0 97 0 92 64 53 — 0 0 — — 0 0 0 0 0 54 — 96 0 — — 0 41 0 95 95 55 — 6 0 — — 0 98 0 41 73 56 — 43 0 — — 0 99 0 28 64 57 — 98 0 — — 0 94 85 85 0 58 — 98 100 — — 89 98 82 100 100 59 — 94 0 — — 0 88 0 68 0 60 — 75 0 — — 0 97 59 79 0 61 — 97 0 — — 0 99 0 38 73 62 — 99 98 — — 84 98 98 99 99 63 — 0 0 — — 0 0 0 0 0 64 — 97 80 — — 0 100 0 95 98 65 — 0 0 — — 0 1 0 58 0 66 — 100 99 — — 0 100 6 100 99 67 — 95 0 — — 0 99 24 95 86 68 — 0 0 — — 0 0 6 0 0 69 — 100 73 — — 60 99 91 99 100 70 — 99 0 — — 0 99 41 85 98 71 — 93 0 — — 0 96 0 91 67 72 — 0 0 — — 0 0 59 0 0 73 — 100 99 — — 64 100 88 100 99 74 — 0 0 — — 0 25 4 0 0 75 — 100 98 — — 98 99 95 99 97 76 — 100 0 — — 0 98 6 0 0 77 — 99 0 — — 0 95 6 97 0 78 — 99 82 — — 0 98 0 89 91 79 — 99 0 — — 0 99 0 55 0 80 — 100 0 — — 0 99 18 86 89 81 — 97 0 — — 0 0 0 27 0 82 — 100 100 — — 40 99 0 68 13 83 — 100 100 — — 89 99 99 96 94 84 — 100 100 — — 78 100 98 100 99 85 — 0 0 — — 0 17 0 19 0 86 — 0 0 — — 0 48 0 0 0 87 — 100 100 — — 95 98 85 99 100 88 — 100 100 — — 99 98 95 99 100 89 — 99 0 — — 0 99 0 0 97 90 — 99 95 — — 84 100 0 98 100 91 — 100 99 — — 95 99 0 100 100 92 — 100 100 — — 99 100 41 99 100 93 — 41 0 — — 0 77 0 9 0 94 — 99 70 — — 29 98 0 9 0 95 — 99 16 — — 0 97 0 0 0 96 — 99 99 — — 99 100 9 99 100 97 — 100 99 — — 95 100 0 99 99 98 — 100 17 — — 69 100 26 99 99 99 — 100 99 — — 100 99 40 100 100 100 — 38 0 — — 0 48 0 41 0 101 — 100 99 — — 100 100 99 99 100 102 — 100 100 — — 98 99 0 100 98 103 — 100 64 — — 0 95 0 91 0 104 — 100 99 — — 97 99 99 99 100 105 — 23 0 — — 0 73 9 0 72 106 — 100 99 — — 90 100 82 99 100 107 —  99*  0* — —  0* 99*  8*  24*  0* 108 — 97 0 — — 0 98 0 16 97 109 — 100 99 — — 97 100 99 100 100 110 — 99 66 — — 98 99 0 97 94 111 — 99 75 — — 90 99 0 97 99 112 — 100 98 — — 99 99 53 100 100 113 — 99 47 — — 0 100 8 95 48 114 — 99 24 — — 69 99 8 99 84 115 — 99 0 — — 0 100 0 91 0 116 — 100 94 — — 73 100 16 97 99 117 — 99 97 — — 82 100 11 98 97 118 — 100 100 — — 98 100 99 100 99 119 — 100 0 — — 0 100 16 99 96 120 — 100 99 — — 94 100 0 99 99 121 — 100 86 — — 82 99 83 100 97 122 — 0 0 — — 0 0 11 0 0 123 — 99 0 — — 40 99 — 80 0 124 — 100 78 — — 60 99 — 96 94 125 — 100 67 — — 60 99 — 92 0 126 — 99 96 — — 60 100 0 94 0 127 — 70 0 — — 0 99 0 68 0 128 — 100 100 — — 97 99 66 100 100 129 — 99 0 — — 0 96 0 0 0 130 — 97 0 — — 0 99 0 19 0 131 — 99 0 — — 0 98 0 86 94 132 — 99 0 — — 0 100 0 94 92 133 — 100 100 — — 60 99 0 100 94 134 — 99 0 — — 0 99 0 41 0 135 — 0 0 — — 0 97 16 74 95 136 — 99 71 — — 86 99 0 99 100 137 — 96 97 — — 78 99 8 100 100 138 — 99 96 — — 84 99 38 100 98 139 — 100 86 — — 100 100 69 99 100 140 — 99 94 — — 87 99 0 96 97 141 — 99 99 — — 98 100 0 99 100 142 — 33 13 — — 20 99 0 95 90 143 — 99 99 — — 100 100 63 100 100 144 — 99 9 — — 40 99 0 98 91 145 — 96 98 — — 100 100 88 100 100 146 — 99 0 — — 0 99 0 97 56 147 — 99 88 — — 100 100 0 98 92 148 — 99 99 — — 100 100 61 100 99 149 — 100 98 — — 100 100 99 100 100 150 — 19 0 — — 60 7 0 74 50 151 — 99 9 — — 0 96 0 54 64 152 — 100 82 — — 87 99 9 97 99 153 — 100 0 — — 73 100 0 96 98 154 — 99 99 — — 97 100 41 100 100 155 — 100 99 — — 100 100 92 100 99 156 — 94 0 — — 0 73 0 41 47 157 — 0 0 — — 0 0 0 54 73 158 — 100 0 — — 0 99 18 99 98 159 — 99 0 — — 0 100 74 99 100 160 — 98 99 — — 0 99 8 100 100 161 — 98 100 — — 0 100 95 100 98 162 — 99 0 — — 0 99 8 98 94 163 — 0 9 — — 0 83 0 88 0 164 — 49 57 — — 0 99 15 9 97 165 — 0 0 — — 0 52 8 0 99 166 — 0 0 — — 0 97 0 68 96 167 — 75 0 — — 0 0 0 0 0 168 — 14 0 — — 0 33 0 0 0 169 — 24 0 — — 0 85 0 0 0 170 — 100 99 — — 99 98 0 100 99 171 — 100 97 — — 0 97 68 99 100 172 — 100 100 — — 87 100 0 99 100 173 — 100 86 — — 0 98 0 83 100 174 — 100 99 — — 0 96 0 97 99 175 — 100 99 — — 82 96 93 99 100 176 — 100 71 — — 0 96 0 68 100 177 — 100 100 — — 73 98 0 83 100 178 — 100 100 — — 80 98 0 83 100 179 — 100 99 — — 73 95 0 93 100 180 — 100 99 — — 0 98 0 68 100 181 — 94 44 — — 0 100 0 60 98 182 — 97 99 — — 87 100 0 95 99 183 — 97 100 — — 67 99 27 94 99 184 — 97 0 — — 0 99 0 82 98 185 — 0 0 — — 0 100 0 74 98 186 — 0 0 — — 0 99 0 54 93 187 — 33 0 — — 0 20 0 9 13 188 — 87 0 — — 0 100 0 97 97 189 — 99 100 — — 80 100 99 99 98 190 — 99 99 — — 80 100 94 100 99 191 — 98 100 — — 0 100 0 97 99 192 — 97 100 — — 73 100 0 99 99 193 — 99 100 — — 0 100 32 99 100 194 — 97 86 — — 0 99 0 91 99 195 — 100 97 — — 60 100 0 98 97 196 — 99 94 — — 73 100 9 98 98 197 — 97 0 — — 95 99 0 79 96 198 — 97 68 — — 0 100 0 94 97 199 — 99 86 — — 0 99 0 68 98 200 — 82 0 — — 0 97 0 0 94 201 — 99 97 — — 20 100 18 97 99 202 — 99 0 — — 0 99 0 28 99 203 — 99 0 — — 0 98 0 96 100 204 — 100* 77* — —  0* 99*  0*  86*  99* 205 — 100 17 — — 0 99 0 91 100 206 — 99 99 — — 84 99 41 99 100 207 — 100 93 — — 64 100 0 99 100 208 — 100 100 — — 99 100 0 99 99 209 — 0 0 — — 0 0 0 0 97 210 — 0 0 — — 0 100 99 94 99 211 — 77 0 — — 0 99 0 17 96 212 — 0 17 — — — 98 0 — — 213 — 97 30 — — 0 85 94 96 100 214 — 98 51 — — 0 100 9 99 100 215 — 89 0 — — 0 98 0 94 99 216 — 96 0 — — 0 76 0 26 99 217 — 75 0 — — 0 83 40 79 99 218 — 94 0 — — 0 99 17 92 87 219 — 70 0 — — 0 0 17 0 0 220 — 98 97 — — 40 98 40 99 100 221 — 98 94 — — 82 100 17 99 100 222 — 99 99 — — 0 100 88 99 100 223 — 96 9 — — 99 100 0 100 100 224 — 99 51 — — 0 100 17 91 100 225 — 65 0 — — 0 99 0 79 98 226 — 99 0 — — 0 96 28 91 100 227 — 87 0 — — 0 99 0 74 98 228 — 99 99 — — 0 99 0 80 99 229 — 99 17 — — 0 99 0 91 98 230 — 99 99 — — 0 100 0 97 100 231 — 98 34 — — 0 100 0 86 100 232 — 100 99 — — 99 100 0 100 100 233 — 100 99 — — 99 100 0 100 100 234 — 99 0 — — 0 99 0 92 84 235 — 84 0 — — 0 17 0 0 79 236 — 97 0 — — 0 96 0 68 97 237 — 99 0 — — 0 97 0 68 97 238 — 99 0 — — 0 0 53 9 43 239 — 99 95 — — 0 67 0 68 100 240 — 100 99 — — 0 99 0 99 100 241 — 99 99 — — 0 100 97 100 100 242 — 99 37 — — 0 100 0 91 100 243 — 100 64 — — 0 100 0 97 100 244 — 82 0 — — 0 91 0 0 96 245 — 90 0 — — 0 97 0 68 93 246 — 99 51 — — 0 100 0 80 100 247 — 100 99 — — 60 100 0 99 100 248 — 99 26 — — 73 100 0 99 100 249 — 40 0 — — 0 99 0 96 100 250 — 98 0 — — 0 77 0 86 100 251 — 99 0 — — 0 98 0 86 100 252 — 100 97 — — 0 100 0 100 100 253 — 99 0 — — 0 0 0 0 76 254 — 100 0 — — 0 84 0 0 64 255 — 100 0 — — 0 0 0 0 39 256 — 99 99 — — 96 100 0 99 100 257 — 100 99 — — 0 100 0 97 98 258 — 41 9 — — 0 89 0 68 90 259 — 98 9 — — 0 100 0 86 97 260 — 0 0 — — 0 0 0 0 0 261 — 0 0 — — 0 0 0 0 47 262 — 99 51 — — 0 0 0 68 99 263 — 100 98 — — 0 100 0 98 100 264 — 100 98 — — 0 92 0 99 98 265 — 100 99 — — 78 100 90 100 100 266 — 100 100 — — 98 100 0 100 100 267 — 100 79 — — 60 100 0 96 93 268 — 95 93 — — 0 99 0 74 0 269 — 80 0 — — 0 67 8 0 0 270 — 92 86 — — 0 91 8 0 81 271 — 100 99 — — 99 100 0 99 98 272 — 100 97 — — 99 99 0 99 99 273 — 0 0 — — 0 72 0 27 43 274 — 8 0 — — 0 96 8 0 69 275 — 97 46 — — 0 99 8 97 99 276 — 100 99 — — 98 100 31 100 100 277 — 100 0 — — 0 100 0 96 98 278 — 99 0 — — 0 99 0 82 100 279 — 100 99 — — 0 100 8 98 100 280 — 99 0 — — 0 96 8 18 87 281 — 98 44 — — 0 — 0 94 98 282 — 99 98 — — 0 — 0 99 100 283 — 99 65 — — 0 — 9 99 100 284 — 99 99 — — 100 — 28 100 100 285 — 98 0 — — 60 — 9 99 99 286 —  98* 85* — — 60* — 100* 100* 100* 288 9 99 52 0 92 0 — — 74 92 289 — 100 0 — — 0 99 0 96 97 290 — 100 99 — — 87 100 0 100 100 291 — 99 0 — — 0 98 0 85 43 292 — 100 99 — — 96 100 92 100 100 293 0 97 47 0 99 0 — — 94 99 294 0 98 0 0 80 0 — — 0 84 296 — 99 0 — — 0 100 0 99 — 297 — 100 99 — — 90 100 0 100 100 298 — 100 93 — — 87 100 0 100 100 299 — 100 95 — — 51 41 100 100 300 — 100 99 — — 82 100 9 99 100 301 — 99 87 — — 87 100 0 98 99 302 —  99*  0* — —  0* 99*  0*  18*  97* 303 — 99 0 — — 0 98 0 92 71 304 — 0 0 — 0 0 16 — 0 0 305 — 99 99 — — 94 100 0 99 99 306 — 7 0 — — 0 93 0 28 64 307 — 0 0 — — 0 0 0 0 0 308 — 81 0 — — 0 98 9 100 0 309 — 97 61 — 92 60 100 — 0 99 310 — 100 99 — — 99 100 0 99 96 311 — 100 0 — — 60 100 0 99 91 313 — 100 97 — — 51 100 91 100 100 314 — 100 95 — — 0 100 94 100 100 315 — 99 99 — — 0 100 0 96 100 316 — 99 0 — — 0 — 9 99 96 318 — 99 0 — — 0 100 0 97 89 319 — 92 88 — — 100 100 0 99 95 320 — 99 67 — — 0 100 0 99 98 321 — 100 99 — — 78 100 9 99 100 322 — 100 93 — — 0 100 99 100 100 323 — 98 0 — — 0 98 0 94 — 324 — 99 83 — — 0 100 63 99 99 325 — 100 0 — — 0 100 0 97 99 326 8 99 99 0 99 73 100 — 99 94 327 — 99 0 — — 0 100 0 96 99 328 — 100 86 — — 0 100 0 98 100 329 — 100 99 — — 69 100 0 100 100 331 — 100 80 — — 73 100 8 100 97 333 — 100 0 — — 0 100 9 74 0 334 — 100 0 — — 0 100 0 97 100 336 — 100 97 — — 95 100 94 100 99 337 — 99 0 — — 0 99 9 41 98 338 — 100 37 — — 40 100 8 100 99 339 — 100 0 — — 0 100 0 98 100 340 — 99 0 — — 0 100 0 91 100 341 — 99 0 — — 0 99 0 99 93 342 — 100 33 — — 99 100 0 100 100 343 — 100 100 — — 97 100 91 100 100 344 — 100 40 — — 87 100 62 100 100 345 — 0 0 — — 0 67 0 9 0 348 — 100 80 — — 94 100 19 100 100 350 — 99 9 — — 0 — 9 96 0 351 — 100 99 — — 92 — 96 100 99 353 — 97 17 — — 0 99 3 99 99 354 — 99 0 — — 0 100 82 98 100 355 — 99 0 — — 0 100 3 91 0 356 — 100 0 — — 0 — 100 100 0 357 — 100 86 — — 87 100 0 99 100 358 — 99 0 — — 0 100 0 97 97 359 — 100 99 — — 97 100 0 100 99 360 — 100 97 — — 95 100 79 100 100 361 — 100 90 — — 0 100 0 100 100 362 — 100 0 — — 0 100 0 96 96 363 — 65 0 — — 0 99 0 96 43 364 — 99 97 — — 88 100 0 99 100 365 — 100 99 — — 64 100 74 100 100 366 — 100 58 — — 0 100 9 99 100 367 — 100 100 — — 100 — 100 100 100 369 — 100 66 — — 0 — 17 100 99 389 — 100 9 — — 0 — 68 98 99 391 — 100 99 — — 73 — 31 99 99 403 — 99 0 — — 0 — 99 100 99 “Cmpd No. ” means compound number and refers to the same compound number as in Index Table A. 

What is claimed is:
 1. A compound selected from Formula 18, N-oxides and salts thereof,

wherein Q¹ is 2-Br-4-F-phenyl, 2-Cl-4-F-phenyl, 2-F-4-Cl-phenyl, 2,4-di-Cl-phenyl, 2,4-di-F-phenyl, 2-Br-6-F-phenyl, 2-Cl-6-F-phenyl, 2,6-di-Cl-phenyl or 2,6-di-F-phenyl; R² is CH₃; and R³³ is CH₃, CH₂CH₃ or CH₂CH₂CH₃.
 2. A compound of claim 1 wherein Q¹ is 2-Br-4-F-phenyl or 2-Cl-4-F-phenyl; R³³ is CH₃ and CH₂CH₃.
 3. A compound of claim 2 wherein Q¹ is 2-Br-4-F-phenyl; and R³³ is CH₃. 